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Xia J, Wang Y, Li X, Liu L, Zhang P, Dai W, Luo P, Wang G, Li Y. The mechanism of perilla oil in regulating lipid metabolism. Food Chem 2025; 476:143318. [PMID: 39977980 DOI: 10.1016/j.foodchem.2025.143318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 02/05/2025] [Accepted: 02/08/2025] [Indexed: 02/22/2025]
Abstract
Emerging science supports the role of lipid metabolism disorders in the occurrence and development of chronic diseases. Dietary intervention has been shown to be an effective strategy for regulating lipid metabolism. Recent studies showed that perilla is rich in various effective ingredients, including fatty acids, flavonoids, and phenolic acids. These ingredients exhibit a myriad of benefits, notably enhancing intestinal health and helping to manage metabolic diseases. Perilla oil stands out as a promising agent for regulating lipid metabolism, underscoring its potential for various health applications. This review introduces the active ingredients in perilla and provides a systematic overview of the mechanism by which perilla oil regulates lipid metabolism to expand its application value. Further research should focus on exploring the dose effect and absorption efficiency of perilla oil in clinical applications.
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Affiliation(s)
- Jiawei Xia
- The Affiliated Hospital of Guizhou Medical University, Guizhou Provincial Engineering Research Center of Ecological Food Innovation, School of Public Health, Guizhou Medical University, Guiyang 561113, China; Guizhou Rapeseed Institute, Guizhou Province Academy of Agricultural Sciences, No. 270-0061 Baiyun Road, Jinyang District, Guiyang, Guizhou 550008, China
| | - Yi Wang
- The Affiliated Hospital of Guizhou Medical University, Guizhou Provincial Engineering Research Center of Ecological Food Innovation, School of Public Health, Guizhou Medical University, Guiyang 561113, China
| | - Xin Li
- The Affiliated Hospital of Guizhou Medical University, Guizhou Provincial Engineering Research Center of Ecological Food Innovation, School of Public Health, Guizhou Medical University, Guiyang 561113, China
| | - Li Liu
- The Affiliated Hospital of Guizhou Medical University, Guizhou Provincial Engineering Research Center of Ecological Food Innovation, School of Public Health, Guizhou Medical University, Guiyang 561113, China
| | - Pin Zhang
- Guizhou Rapeseed Institute, Guizhou Province Academy of Agricultural Sciences, No. 270-0061 Baiyun Road, Jinyang District, Guiyang, Guizhou 550008, China
| | - Wendong Dai
- Guizhou Rapeseed Institute, Guizhou Province Academy of Agricultural Sciences, No. 270-0061 Baiyun Road, Jinyang District, Guiyang, Guizhou 550008, China
| | - Peng Luo
- The Affiliated Hospital of Guizhou Medical University, Guizhou Provincial Engineering Research Center of Ecological Food Innovation, School of Public Health, Guizhou Medical University, Guiyang 561113, China
| | - Guoze Wang
- The Affiliated Hospital of Guizhou Medical University, Guizhou Provincial Engineering Research Center of Ecological Food Innovation, School of Public Health, Guizhou Medical University, Guiyang 561113, China.
| | - Yanhong Li
- The Affiliated Hospital of Guizhou Medical University, Guizhou Provincial Engineering Research Center of Ecological Food Innovation, School of Public Health, Guizhou Medical University, Guiyang 561113, China.
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Hedayati S, Doustmohammadian A, Jambarsang S, Maadi M, Zamani F, Hosseinzadeh M. Dietary lipophilic index and odds of metabolic dysfunction-associated steatotic liver disease (MASLD): A population-based study. Dig Liver Dis 2025:S1590-8658(25)00312-3. [PMID: 40368699 DOI: 10.1016/j.dld.2025.04.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2025] [Revised: 03/29/2025] [Accepted: 04/01/2025] [Indexed: 05/16/2025]
Abstract
INTRODUCTION Non-alcoholic fatty liver disease (MASLD) is one of the highly prevalent metabolic disorders worldwide The present study aimed to determine the association between a novel dietary lipophilic index (LI) with metabolic profile and MASLD in a population-based study in Amol, Iran. PATIENTS AND METHODS A cross-sectional study was conducted among 2979 Iranian adults within the framework of the Amol cohort study (AmolCS) Dietary assessments were performed using a validated 168-item food frequency questionnaire (FFQ) The dietary fatty acids were determined using the food composition table in Food Data Central of the USDA to indicate the lipophilic index Information about the melting point of fatty acids was obtained from the lipid bank database MASLD was defined as the ultrasound detection of hepatic steatosis that ruled out other causes of hepatic fat accumulation Then, dietary LI and lipophilic load (LL) were calculated using dietary fatty acid intake and melting point Multivariate MASLD The analysis was carried out for all participants stratified by sex and BMI Potential confounders were included in three different adjusted models. RESULTS The results revealed that dietary LI was associated with higher BMI and (WHtR), low physical activity, being female, living in urban residencies, and diabetes After adjustment for potential confounders, age, and energy intake, the odds ratio of MASLD in women was 1.33 (95 % CI: 1.05-1.99, p = 0.048) in the last tertile of dietary LI compared to the first tertile In adjustment by age and energy intake, chronic disease, smoking, physical activity, waist circumference, and residency women have a higher chance of MASLD in the second tertile of dietary LI (OR:1.38 95 % CI: 1.01-1.89) as well as in the third LI (OR:1.39, 95 % CI: 1.02-1.91) compared to the first tertile When the body mass index (BMI) was added to other confounders variables, the odds ratio of MASLD was 1.44 (95 % CI: 1.05-1.99) in the second tertile of LI and 1.41(95 % CI:1.02-1.95) in the third tertiles, Ptrend=0.04 In normal weight participants (BMI< 25), after adjustment for age and energy intake, the odds of MASLD were 86 % higher (CI; 1.07-3.25, Ptrend< 0.03) in the last tertile of LL compared to the first one. CONCLUSIONS This study found that higher levels of dietary fatty acids are associated with 40 % higher odds of MASLD in women Additionally, higher levels of fatty acids in normal-weight individuals were linked to an 86 % higher chance of MASLD It is highly recommended to reduce intake of saturated fatty acids and trans fatty acids, which are associated with a lower risk of MASLD.
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Affiliation(s)
- Safoora Hedayati
- International campus of shahidsadoughiUniversity of Medical Sciences, Yazd, Iran; Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Azam Doustmohammadian
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Sara Jambarsang
- Center for Healthcare Data Modeling, Departments of Biostatistics and Epidemiology, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mansooreh Maadi
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Farhad Zamani
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran.
| | - Mahdieh Hosseinzadeh
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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Gong X, Bai S, Lei E, Lu T, Chen Y, Cai J, Liu J. A bibliometric analysis of metabolic dysfunction-associated steatotic liver disease in children from 2004 to 2024. Front Pediatr 2025; 13:1468788. [PMID: 40356777 PMCID: PMC12066688 DOI: 10.3389/fped.2025.1468788] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 04/14/2025] [Indexed: 05/15/2025] Open
Abstract
Background Metabolic dysfunction-associated steatotic liver disease (MASLD), once known as Non-alcoholic fatty liver disease, impacts between 3% and 10% of children and adolescents globally, as well as nearly one-third of obsessed boys and one-quarter of obsessed girls, and is the most frequent cause of pediatric liver disease associated with the obesity epidemic. With the growing attention and increasing volume of literature on pediatric MASLD, there is an urgent need for bibliometric analysis and visualization in the area of pediatric MASLD study in terms of dissecting study priorities. Methods Literature was searched in the Web of Science Core Collection database, followed by categorization, bibliometric study as well as visual analysis conducted by applying software including Citespace, VOSviewer, and the R language. The study concentrated on analyzing information related to key authors, spatial and temporal distribution, core keywords, and important citations. Results In total, 3,409 publications on pediatric MASLD were collected in the study, including 2,697 articles and 712 review articles. Between 2004 and 2024, the volume of publications had been constantly increasing per year. The country with the most numerous publications was the United States, which had extensive exchanges and collaborations with Italy, China, and England, followed by Italy. The Journal of Pediatric Gastroenterology and Nutrition had the greatest quantity of publications in this domain. The core literature was a clinical guideline. Insulin resistance, metabolic syndrome, steatohepatitis, hepatocellular carcinoma, cardiovascular risk, diabetes risk, diagnostic accuracy, lifestyle intervention, gut microbiome, probiotics, and metabolic dysfunction-associated steatotic liver disease were also hot topics and frontier trends in pediatric MASLD studies. Conclusion This research represents the inaugural application of bibliometric analysis to examine the developmental trajectory of pediatric MASLD studies over the past two decades, which reveals that the etiology, pathological changes of the liver, relationship with obesity, complications, comorbidities, diagnosis and treatments of pediatric MASLD are the key focuses and provides academic references for pediatric clinicians and scholars to grasp the hotspots, the cutting edge and the evolving trends in the area.
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Affiliation(s)
- Xiaowei Gong
- College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
- Department of Pediatrics, Wuhan Hospital of Traditional Chinese Medicine, Wuhan, China
| | - Siyu Bai
- College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
| | - Enze Lei
- College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
| | - Tao Lu
- College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
| | - Yao Chen
- Department of Pediatrics, Hubei Provincial Hospital of Traditional Chinese Medicine, Affiliated Hospital of Hubei University of Chinese Medicine, Wuhan, China
- Hubei Shizhen Laboratory, Wuhan, China
- Hubei Key Laboratory of Liver and Kidney Research and Application of Traditional Chinese Medicine, Wuhan, China
| | - Jianxin Cai
- Department of Pediatrics, Wuhan Hospital of Traditional Chinese Medicine, Wuhan, China
| | - Jianzhong Liu
- College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
- Department of Pediatrics, Hubei Provincial Hospital of Traditional Chinese Medicine, Affiliated Hospital of Hubei University of Chinese Medicine, Wuhan, China
- Hubei Shizhen Laboratory, Wuhan, China
- Hubei Key Laboratory of Liver and Kidney Research and Application of Traditional Chinese Medicine, Wuhan, China
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Gonzalez FM. Hepatorenal syndrome: Paving a pathway from a fatal condition to an opportunity to preserve kidney function. World J Nephrol 2025; 14:101861. [PMID: 40134651 PMCID: PMC11755242 DOI: 10.5527/wjn.v14.i1.101861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 11/12/2024] [Accepted: 12/02/2024] [Indexed: 01/20/2025] Open
Abstract
In the 19th century, von Frerichs F and Flint A identified a type of acute renal impairment associated with advanced liver disease, characterized by oliguria, absence of proteinuria, and normal renal histology, which was later termed hepatorenal syndrome (HRS). HRS primarily affects cirrhotic patients with ascites and often follows severe infections, digestive hemorrhages, or high-volume paracentesis. Pathophysiologically, HRS involves low glomerular filtration rate, hypotension, renin-angiotensin axis activation, water clearance, hyponatremia, and minimal urinary sodium excretion. These conditions mimic those seen in decreased effective circulatory volume (ECV) scenarios such as septic shock or heart failure. HRS represents a specific form of prerenal acute kidney injury (AKI) in patients with baseline renal ischemia, where the kidney attempts to correct decreased ECV by retaining sodium and water. Intense renal vasoconstriction, passive hyperemia from ascites, and acute tubular necrosis (ATN) with specific urinary sediment changes are observed. Persistent oliguria may transition HRS to ATN, although this shift is less straightforward than in other prerenal AKI contexts. Notably, liver grafts from HRS patients can recover function more rapidly than those from other ischemic conditions. Experimental studies, such as those by Duailibe et al, using omega-3 fatty acids in cirrhotic rat models, have shown promising results in reducing oxidative stress and improving kidney function. These findings suggest potential therapeutic strategies and underscore the need for further research to understand the mechanisms of HRS and explore possible treatments. Future research should address the impact of omega-3 on survival and secondary outcomes, as well as consider the balance of therapeutic risks and benefits in severe liver disease.
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Affiliation(s)
- Fernando M Gonzalez
- Department of Nephrology, Faculty of Medicine, Universidad de Chile, Santiago 7500922, Chile
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Zhao M, He Q, Shu X, Xu R, Zhang Z, Mou Y, Liao W, Zhang Y, Zhou Z, Shen T. Zhuyu pill attenuates metabolic-associated fatty liver disease by regulating macrophage polarization through TLR4 signaling pathway. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2025; 138:156439. [PMID: 39892308 DOI: 10.1016/j.phymed.2025.156439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 01/27/2025] [Accepted: 01/27/2025] [Indexed: 02/03/2025]
Abstract
BACKGROUND Metabolic-associated fatty liver disease (MAFLD) is the leading chronic liver disease globally, impacting a large segment of the population. The Zhuyu Pill (ZYP), a traditional Chinese remedy, has been clinically used for treating MAFLD, with its effectiveness demonstrated in both human patients and animal models. However, the underlying mechanisms of how ZYP addresses MAFLD still require further investigation. OBJECTIVE This study investigated the molecular mechanism of ZYP in treating MAFLD through both in vivo and vitro methods. METHODS A murine MAFLD model was induced by a high-fat, high-fructose diet for 12 weeks. ZYP was administered for 4 weeks, with fenofibrate serving as a positive control. Indicators of lipid metabolism in serum and liver tissue were detected by automatic biochemical analyzer and ELISA, respectively. Histopathological evaluation of liver sections was performed using HE and oil red O staining. Transcriptomics was employed to further investigate the therapeutic mechanism of ZYP in MAFLD. Additionally, macrophages and their polarization in the liver were analyzed using ELISA, flow cytometry, immunohistochemistry, and immunofluorescence (IF). Candidate proteins and pathways were validated in vivo and in vitro by western blotting and IF. Validation of the pathway was performed in vitro using inhibitors and co-culture strategies. RESULTS ZYP significantly improved obesity and hepatic steatosis in MAFLD mice, reducing body/liver weight and regulating lipid metabolism indicators in serum and liver tissue. Bioinformatics analysis of transcriptomic data highlighted lipid metabolism regulation and inflammation control as key effects of ZYP in treating MAFLD. The in vivo experimental results showed that ZYP inhibited M1 polarization of macrophages (pro-inflammatory) and promoted M2 polarization of macrophages (anti-inflammatory) in MAFLD mice. Further in vivo and vitro experiments indicated that ZYP competes with LPS to bind to Toll-like receptor 4 (TLR4), suppressing M1 polarization in liver macrophages, and improving MAFLD. The in vitro co-culture system also confirmed that ZYP reduces liver lipid deposition by modulating M1 macrophage polarization. CONCLUSIONS ZYP alleviates MAFLD by inhibiting M1 polarization of liver macrophages, indicating that ZYP may be a promising treatment for MAFLD. Its mechanism of action is to inhibit the TLR4/MyD88/TRAF6 signaling pathway, modulate macrophage polarization, and improve inflammatory response.
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Affiliation(s)
- Mei Zhao
- Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China
| | - Qingman He
- Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China
| | - Xinyao Shu
- Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China
| | - Ruitong Xu
- Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China
| | - Zhongyi Zhang
- Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China
| | - Yu Mou
- Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China
| | - Wenhao Liao
- Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China
| | - Yong Zhang
- Institute of Traditional Chinese Medicine, Sichuan Academy of Chinese Medicine Sciences, Chengdu, 610014, PR China.
| | - Zubing Zhou
- Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China.
| | - Tao Shen
- Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China.
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Iturbe-Rey S, Maccali C, Arrese M, Aspichueta P, Oliveira CP, Castro RE, Lapitz A, Izquierdo-Sanchez L, Bujanda L, Perugorria MJ, Banales JM, Rodrigues PM. Lipotoxicity-driven metabolic dysfunction-associated steatotic liver disease (MASLD). Atherosclerosis 2025; 400:119053. [PMID: 39581063 DOI: 10.1016/j.atherosclerosis.2024.119053] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 10/19/2024] [Accepted: 11/08/2024] [Indexed: 11/26/2024]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a spectrum of liver lesions, ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), that may further progress to cirrhosis. MASLD is estimated to affect more than one third of the general population and it represents a risk factor for end-stage liver failure and liver cancer, substantially contributing to liver-related morbidity and mortality. Although the pathogenesis of MASLD is incompletely understood, it is known to consist of a multifactorial process influenced by extrinsic and intrinsic factors such as metabolic, environmental and demographic features, gut microbiota and genetics. Dysregulation of both extracellular and intracellular lipid composition is known to promote the generation of toxic lipid species, thereby triggering lipotoxicity and cellular stress. These events ultimately lead to the activation of distinct cell death pathways, resulting in inflammation, fibrogenesis and, eventually, carcinogenesis. In this manuscript, we provide a comprehensive review of the role of lipotoxicity during MASLD pathogenesis, discussing the most relevant lipid species and related molecular mechanisms, summarizing the cell type-specific effects and highlighting the most promising putative therapeutic strategies for modulating lipotoxicity and lipid metabolism in MASLD.
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Affiliation(s)
- Santiago Iturbe-Rey
- Department of Liver and Gastrointestinal Diseases, Biogipuzkoa Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), Donostia-San Sebastian, Spain
| | - Claudia Maccali
- Clinical and Experimental Gastroenterology Laboratory LIM-07, Department of Gastroenterology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Marco Arrese
- Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile Santiago, 8330077, Chile
| | - Patricia Aspichueta
- Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940, Leioa, Spain; Biobizkaia Health Research Institute, Cruces University Hospital, 48903, Barakaldo, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), Spain
| | - Claudia P Oliveira
- Clinical and Experimental Gastroenterology Laboratory LIM-07, Department of Gastroenterology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; Division of Clinical Gastroenterology and Hepatology, Hospital das Clínicas de São Paulo, HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Rui E Castro
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
| | - Ainhoa Lapitz
- Department of Liver and Gastrointestinal Diseases, Biogipuzkoa Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), Donostia-San Sebastian, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), Spain
| | - Laura Izquierdo-Sanchez
- Department of Liver and Gastrointestinal Diseases, Biogipuzkoa Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), Donostia-San Sebastian, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), Spain
| | - Luis Bujanda
- Department of Liver and Gastrointestinal Diseases, Biogipuzkoa Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), Donostia-San Sebastian, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), Spain
| | - Maria J Perugorria
- Department of Liver and Gastrointestinal Diseases, Biogipuzkoa Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), Donostia-San Sebastian, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), Spain; Department of Medicine, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940, Leioa, Spain
| | - Jesus M Banales
- Department of Liver and Gastrointestinal Diseases, Biogipuzkoa Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), Donostia-San Sebastian, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain; Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain.
| | - Pedro M Rodrigues
- Department of Liver and Gastrointestinal Diseases, Biogipuzkoa Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), Donostia-San Sebastian, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
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Ghavidel F, Hashemy SI, Aliari M, Rajabian A, Tabrizi MH, Atkin SL, Jamialahmadi T, Hosseini H, Sahebkar A. The Effects of Resveratrol Supplementation on the Metabolism of Lipids in Metabolic Disorders. Curr Med Chem 2025; 32:2219-2234. [PMID: 37828670 DOI: 10.2174/0109298673255218231005062112] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 06/25/2023] [Accepted: 08/26/2023] [Indexed: 10/14/2023]
Abstract
Lipids are stored energy sources in animals, and disturbance of lipid metabolism is associated with metabolic disorders, including cardiovascular diseases, obesity, nonalcoholic fatty liver disease, and diabetes. Modifying dysregulated lipid metabolism homeostasis can lead to enhanced therapeutic benefits, such as the use of statin therapy in cardiovascular disease. However, many natural compounds may have therapeutic utility to improve lipid metabolism. Resveratrol is a polyphenol extracted from dietary botanicals, including grapes and berries, which has been reported to affect many biological processes, including lipid metabolism. This review evaluates the effects of resveratrol on lipid metabolism dysregulation affecting atherosclerosis, diabetes, and nonalcoholic fatty liver disease (NAFLD). In addition, it details the mechanisms by which resveratrol may improve lipid metabolism homeostasis.
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Affiliation(s)
- Farideh Ghavidel
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed Isaac Hashemy
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahdeyeh Aliari
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Arezoo Rajabian
- Department of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Stephen L Atkin
- Research Department, Royal College of Surgeons in Ireland Bahrain, Adliya, Bahrain
| | - Tannaz Jamialahmadi
- International UNESCO center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hossein Hosseini
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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Taha M, Abdelbagi O, Baokbah TAS, Bagadood RM, Jalal NA, Obaid R, Al-Hazmi NE, Qusty NF. Insights into the protective effect of omega-3 nanoemulsion against colistin-induced nephrotoxicity in experimental rats: regulation of autophagy and necroptosis via AMPK/mTOR and RIPK1/RIPK3/MLKL signaling pathways. Ren Fail 2024; 46:2429686. [PMID: 39584420 PMCID: PMC11590192 DOI: 10.1080/0886022x.2024.2429686] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2024] [Revised: 10/24/2024] [Accepted: 11/10/2024] [Indexed: 11/26/2024] Open
Abstract
Colistin is considered one of the most effective antibiotics against gram-negative bacteria. However, nephrotoxicity is one of the dose-limiting factors in its treatment. This study aimed to evaluate the outcome of omega-3 nanoemulsion against colistin-induced nephrotoxicity and its possible underlying mechanism. Four rat groups were involved in the present research; each group containing ten rats was divided as follows: Group I (control) rats received normal saline; Group II (omega-3 nanoemulsion) rats received a dose of 500 mg/kg/body weight orally; Group III (colistin) rats received colistin intraperitoneally (300.000 IU/kg/day); and Group IV (colistin/omega-3 nanoemulsion) rats were treated for six days. The results revealed that colistin administration caused deterioration in renal functions such as creatinine, blood urea nitrogen, 24 h proteinuria, and kidney injury molecule-1 with decrease in creatinine clearance, resulting in histological alternation and tubular damage with diffuse interstitial inflammation. Additionally, colistin significantly increased the lipid peroxidation marker malonaldehyde, proinflammatory cytokines tumor necrosis alpha, interleukin-6, interleukin-1 beta. Also, autophagy influx marker microtubule-associated protein light chain 3B, Beclin-1, and necroptotic related proteins, receptor-interacting protein kinase-3 (RIPK-3), RIPK-1, mixed lineage kinase domain-like protein, and autophagy pathway regulatory kinase AMP-activated protein kinase, with a decrease in antioxidant enzymes catalase, superoxide dismutase, and total antioxidant capacity, autophagic marker ubiquitin-binding protein (p62), and regulator Mammalian target of rapamycin. Interestingly, omega-3 nanoemulsion reversed the results above, dramatically improving renal function and histological picture. Thus, omega-3 nanoemulsion provided a notable method for suppressing colistin-induced nephrotoxicity via its antioxidant and anti-inflammatory power, inhibiting pathological autophagy and necroptosis.
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Affiliation(s)
- Medhat Taha
- Department of Anatomy, Al-Qunfudah Medical College, Umm Al-Qura University, Al-Qunfudhah, Saudi Arabia
- Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Omer Abdelbagi
- Department of Pathology, Qunfudah Faculty of Medicine, Umm-Al-Qura University, Al-Qunfudhah, Saudi Arabia
| | - Tourki A. S. Baokbah
- Department of Medical Emergency Services, College of Health Sciences-AlQunfudah, Umm Al-Qura University, Al-Qunfudhah, Saudi Arabia
| | - Rehab M. Bagadood
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al–Qura University, Makkah, Saudi Arabia
| | - Naif A. Jalal
- Department of Microbiology and Parasitology, Faculty of Medicine, Umm Al‐Qura University, Makkah, Saudi Arabia
| | - Rami Obaid
- Department of Medical Genetics, Faculty of Medicine at Al-Qunfudah, Umm Al-Qura University, Al-Qunfudhah, Saudi Arabia
| | - Nawal E. Al-Hazmi
- Department of Chemistry, Division of Biology (Microbiology), University College of Qunfudah, Umm Al-Qura University, Al-Qunfudhah, Saudi Arabia
| | - Naeem F. Qusty
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al–Qura University, Makkah, Saudi Arabia
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Sun Y, Xu H, Ye K. Genome-wide association studies and multi-omics integrative analysis reveal novel loci and their molecular mechanisms for circulating polyunsaturated, monounsaturated, and saturated fatty acids. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.11.11.24317110. [PMID: 39606376 PMCID: PMC11601680 DOI: 10.1101/2024.11.11.24317110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/29/2024]
Abstract
Previous genome-wide association studies (GWAS) have identified genetic loci associated with the circulating levels of FAs, but the biological mechanisms of these genetic associations remain largely unexplored. Here, we conducted GWAS to identify additional genetic loci for 19 circulating fatty acid (FA) traits in UK Biobank participants of European ancestry (N = 239,268) and five other ancestries (N = 508 - 4,663). We leveraged the GWAS findings to characterize genetic correlations and colocalized regions among FAs, explore sex differences, examine FA loci influenced by lipoprotein metabolism, and apply statistical fine-mapping to pinpoint putative causal variants. We integrated GWAS signals with multi-omics quantitative trait loci (QTL) to reveal intermediate molecular phenotypes mediating the associations between the genetic loci and FA levels. Altogether, we identified 215 significant loci for polyunsaturated fatty acids (PUFAs)-related traits in European participants, 163 loci for monounsaturated fatty acids (MUFAs)-related traits, and 119 loci for saturated fatty acids (SFAs)-related traits, including 70, 61, and 54 novel loci, respectively. A novel locus for total FAs, the percentage of omega-6 PUFAs in total FAs, and total MUFAs (around genes GSTT1/2/2B) overlapped with QTL signals for all six molecular phenotypes examined, including gene expression, protein abundance, DNA methylation, splicing, histone modification, and chromatin accessibility. Across 19 FA traits, 65% of GWAS loci overlapped with QTL signals for at least one molecular phenotype. Our study identifies novel genetic loci for circulating FA levels and systematically uncovers their underlying molecular mechanisms.
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Affiliation(s)
- Yitang Sun
- Department of Genetics, University of Georgia, Athens, GA, USA
| | - Huifang Xu
- Department of Genetics, University of Georgia, Athens, GA, USA
| | - Kaixiong Ye
- Department of Genetics, University of Georgia, Athens, GA, USA
- Institute of Bioinformatics, University of Georgia, Athens, GA, USA
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10
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Ali GF, Hassanein EHM, Mohamed WR. Molecular mechanisms underlying methotrexate-induced intestinal injury and protective strategies. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:8165-8188. [PMID: 38822868 PMCID: PMC11522073 DOI: 10.1007/s00210-024-03164-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Accepted: 05/13/2024] [Indexed: 06/03/2024]
Abstract
Methotrexate (MTX) is a folic acid reductase inhibitor that manages various malignancies as well as immune-mediated inflammatory chronic diseases. Despite being frequently prescribed, MTX's severe multiple toxicities can occasionally limit its therapeutic potential. Intestinal toxicity is a severe adverse effect associated with the administration of MTX, and patients are significantly burdened by MTX-provoked intestinal mucositis. However, the mechanism of such intestinal toxicity is not entirely understood, mechanistic studies demonstrated oxidative stress and inflammatory reactions as key factors that lead to the development of MTX-induced intestinal injury. Besides, MTX causes intestinal cells to express pro-inflammatory cytokines like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which activate nuclear factor-kappa B (NF-κB). This is followed by the activation of the Janus kinase/signal transducer and activator of the transcription3 (JAK/STAT3) signaling pathway. Moreover, because of its dual anti-inflammatory and antioxidative properties, nuclear factor erythroid-2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) has been considered a critical signaling pathway that counteracts oxidative stress in MTX-induced intestinal injury. Several agents have potential protective effects in counteracting MTX-provoked intestinal injury such as omega-3 polyunsaturated fatty acids, taurine, umbelliferone, vinpocetine, perindopril, rutin, hesperidin, lycopene, quercetin, apocynin, lactobacillus, berberine, zinc, and nifuroxazide. This review aims to summarize the potential redox molecular mechanisms of MTX-induced intestinal injury and how they can be alleviated. In conclusion, studying these molecular pathways might open the way for early alleviation of the intestinal damage and the development of various agent plans to attenuate MTX-mediated intestinal injury.
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Affiliation(s)
- Gaber F Ali
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni Suef, 62514, Egypt
| | - Emad H M Hassanein
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Assiut Branch, Al-Azhar University, Assiut, 71524, Egypt
| | - Wafaa R Mohamed
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni Suef, 62514, Egypt.
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11
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Perna A, Venditti N, Merolla F, Fusco S, Guerra G, Zoroddu S, De Luca A, Bagella L. Nutraceuticals in Pregnancy: A Special Focus on Probiotics. Int J Mol Sci 2024; 25:9688. [PMID: 39273635 PMCID: PMC11395456 DOI: 10.3390/ijms25179688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 08/30/2024] [Accepted: 09/04/2024] [Indexed: 09/15/2024] Open
Abstract
The placenta is crucial to fetal development and performs vital functions such as nutrient exchange, waste removal and hormone regulation. Abnormal placental development can lead to conditions such as fetal growth restriction, pre-eclampsia and stillbirth, affecting both immediate and long-term fetal health. Placental development is a highly complex process involving interactions between maternal and fetal components, imprinted genes, signaling pathways, mitochondria, fetal sexomes and environmental factors such as diet, supplementation and exercise. Probiotics have been shown to make a significant contribution to prenatal health, placental health and fetal development, with associations with reduced risk of preterm birth and pre-eclampsia, as well as improvements in maternal health through effects on gut microbiota, lipid metabolism, vaginal infections, gestational diabetes, allergic diseases and inflammation. This review summarizes key studies on the influence of dietary supplementation on placental development, with a focus on the role of probiotics in prenatal health and fetal development.
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Affiliation(s)
- Angelica Perna
- Department of Medicine and Health Sciences "Vincenzo Tiberio", University of Molise, Via F. De Sanctis, 86100 Campobasso, Italy
| | - Noemi Venditti
- Department of Medicine and Health Sciences "Vincenzo Tiberio", University of Molise, Via F. De Sanctis, 86100 Campobasso, Italy
- UO Laboratory Analysis, Responsible Research Hospital, Largo Agostino Gemelli, 1, 86100 Campobasso, Italy
| | - Francesco Merolla
- Department of Medicine and Health Sciences "Vincenzo Tiberio", University of Molise, Via F. De Sanctis, 86100 Campobasso, Italy
| | - Sabato Fusco
- Department of Medicine and Health Sciences "Vincenzo Tiberio", University of Molise, Via F. De Sanctis, 86100 Campobasso, Italy
| | - Germano Guerra
- Department of Medicine and Health Sciences "Vincenzo Tiberio", University of Molise, Via F. De Sanctis, 86100 Campobasso, Italy
| | - Stefano Zoroddu
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/b, 07100 Sassari, Italy
| | - Antonio De Luca
- Department of Mental and Physical Health and Preventive Medicine, Section of Human Anatomy, University of Campania "Luigi Vanvitelli", Via Costantinopoli 16, 80138 Naples, Italy
| | - Luigi Bagella
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/b, 07100 Sassari, Italy
- Sbarro Institute for Cancer Research and Molecular Medicine, Centre for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA
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12
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Jacob T, Sindhu S, Hasan A, Malik MZ, Arefanian H, Al-Rashed F, Nizam R, Kochumon S, Thomas R, Bahman F, Shenouda S, Wilson A, Akther N, Al-Roub A, Abukhalaf N, Albeloushi S, Abu-Farha M, Al Madhoun A, Alzaid F, Thanaraj TA, Koistinen HA, Tuomilehto J, Al-Mulla F, Ahmad R. Soybean oil-based HFD induces gut dysbiosis that leads to steatosis, hepatic inflammation and insulin resistance in mice. Front Microbiol 2024; 15:1407258. [PMID: 39165573 PMCID: PMC11334085 DOI: 10.3389/fmicb.2024.1407258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Accepted: 07/09/2024] [Indexed: 08/22/2024] Open
Abstract
High-fat diets (HFDs) shape the gut microbiome and promote obesity, inflammation, and liver steatosis. Fish and soybean are part of a healthy diet; however, the impact of these fats, in the absence of sucrose, on gut microbial dysbiosis and its association with liver steatosis remains unclear. Here, we investigated the effect of sucrose-free soybean oil-and fish oil-based high fat diets (HFDs) (SF-Soy-HFD and SF-Fish-HFD, respectively) on gut dysbiosis, obesity, steatosis, hepatic inflammation, and insulin resistance. C57BL/6 mice were fed these HFDs for 24 weeks. Both diets had comparable effects on liver and total body weights. But 16S-rRNA sequencing of the gut content revealed induction of gut dysbiosis at different taxonomic levels. The microbial communities were clearly separated, showing differential dysbiosis between the two HFDs. Compared with the SF-Fish-HFD control group, the SF-Soy-HFD group had an increased abundance of Bacteroidetes, Firmicutes, and Deferribacteres, but a lower abundance of Verrucomicrobia. The Clostridia/Bacteroidia (C/B) ratio was higher in the SF-Soy-HFD group (3.11) than in the SF-Fish-HFD group (2.5). Conversely, the Verrucomicrobiacae/S24_7 (also known as Muribaculaceae family) ratio was lower in the SF-Soy-HFD group (0.02) than that in the SF-Fish-HFD group (0.75). The SF-Soy-HFD group had a positive association with S24_7, Clostridiales, Allobaculum, Coriobacteriaceae, Adlercreutzia, Christensenellaceae, Lactococcus, and Oscillospira, but was related to a lower abundance of Akkermansia, which maintains gut barrier integrity. The gut microbiota in the SF-Soy-HFD group had predicted associations with host genes related to fatty liver and inflammatory pathways. Mice fed the SF-Soy-HFD developed liver steatosis and showed increased transcript levels of genes associated with de novo lipogenesis (Acaca, Fasn, Scd1, Elovl6) and cholesterol synthesis (Hmgcr) pathways compared to those in the SF-Fish-HFD-group. No differences were observed in the expression of fat uptake genes (Cd36 and Fabp1). The expression of the fat efflux gene (Mttp) was reduced in the SF-Soy-HFD group. Moreover, hepatic inflammation markers (Tnfa and Il1b) were notably expressed in SF-Soy-HFD-fed mice. In conclusion, SF-Soy-HFD feeding induced gut dysbiosis in mice, leading to steatosis, hepatic inflammation, and impaired glucose homeostasis.
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Affiliation(s)
- Texy Jacob
- Dasman Diabetes Institute, Dasman, Kuwait
| | | | - Amal Hasan
- Dasman Diabetes Institute, Dasman, Kuwait
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Fawaz Alzaid
- Dasman Diabetes Institute, Dasman, Kuwait
- INSERM UMR-S1151, CNRS UMR-S8253, Institut Necker Enfants Malades, Université Paris Cité, Paris, France
| | | | - Heikki A. Koistinen
- Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
- Minerva Foundation Institute for Medical Research, Helsinki, Finland
| | - Jaakko Tuomilehto
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
- Department of Public Health, University of Helsinki, Helsinki, Finland
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Ahmed DH, Fateh HL. Impact of flaxseed supplementation on lipid profile and liver enzymes in patients with non-alcoholic fatty liver disease: Systematic review and meta-analysis of randomized controlled trials. Prostaglandins Other Lipid Mediat 2024; 173:106838. [PMID: 38663513 DOI: 10.1016/j.prostaglandins.2024.106838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Revised: 04/18/2024] [Accepted: 04/21/2024] [Indexed: 05/07/2024]
Abstract
Since the effects of flaxseed supplementation on lipid profile and liver enzymes are still controversial, a meta-analysis of randomized controlled trials was conducted in the present study to assess the effect of flaxseed supplementation on lipid profile and liver enzymes. The study was designed, conducted, and reported according to the guidelines of the 2020 preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement. A systematic and comprehensive search was performed in several databases from inception up to January 10, 2024. The meta-analysis on the impact of flaxseed supplementation on lipid profile and liver enzymes indicates that the overall effect of flaxseed supplementation on triglycerides, combining different doses, revealed a significant reduction with a WMD of - 230.72 (-53.95, - 27.49) and a P-value of 0.010. High-density lipoprotein (HDL) demonstrated a positive effect, with an overall WMD of 1.82 (0.27, 3.38) and a P-value of 0.021, indicating an increase in HDL levels. The liver enzymes AST and ALT displayed reductions in their levels, with overall WMDs of - 21.18 (-2.95, 0.59) and - 24.83 (-8.74, - 20.91), respectively. Subgroup analysis based on dosage revealed more pronounced reductions in ALT levels for doses below 2000 mg/day. Findings from this study suggest that a flaxseed supplement might be beneficial to modulate the blood lipid profile and liver enzymes.
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Affiliation(s)
- Dyari H Ahmed
- Nursing Department, Halabja Technical Institute, Sulaimani Polytechnic University, Sulaimani, Iraq
| | - Hawal Lateef Fateh
- Nursing Department, Kalar Technical Institute, Garmian Polytechnic University, Kalar, Iraq.
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14
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Li X, Liu C, Zhang R, Li Y, Ye D, Wang H, He M, Sun Y. Biosynthetic deficiency of docosahexaenoic acid causes nonalcoholic fatty liver disease and ferroptosis-mediated hepatocyte injury. J Biol Chem 2024; 300:107405. [PMID: 38788853 PMCID: PMC11231757 DOI: 10.1016/j.jbc.2024.107405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 05/07/2024] [Accepted: 05/08/2024] [Indexed: 05/26/2024] Open
Abstract
Exogenous omega-3 fatty acids, particularly docosahexaenoic acid (DHA), have shown to exert beneficial effects on nonalcoholic fatty liver disease (NAFLD), which is characterized by the excessive accumulation of lipids and chronic injury in the liver. However, the effect of endogenous DHA biosynthesis on the lipid homeostasis of liver is poorly understood. In this study, we used a DHA biosynthesis-deficient zebrafish model, elovl2 mutant, to explore the effect of endogenously biosynthesized DHA on hepatic lipid homeostasis. We found the pathways of lipogenesis and lipid uptake were strongly activated, while the pathways of lipid oxidation and lipid transport were inhibited in the liver of elovl2 mutants, leading to lipid droplet accumulation in the mutant hepatocytes and NAFLD. Furthermore, the elovl2 mutant hepatocytes exhibited disrupted mitochondrial structure and function, activated endoplasmic reticulum stress, and hepatic injury. We further unveiled that the hepatic cell death and injury was mainly mediated by ferroptosis, rather than apoptosis, in elovl2 mutants. Elevating DHA content in elovl2 mutants, either by the introduction of an omega-3 desaturase (fat1) transgene or by feeding with a DHA-rich diet, could strongly alleviate NAFLD features and ferroptosis-mediated hepatic injury. Together, our study elucidates the essential role of endogenous DHA biosynthesis in maintaining hepatic lipid homeostasis and liver health, highlighting that DHA deficiency can lead to NAFLD and ferroptosis-mediated hepatic injury.
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Affiliation(s)
- Xuehui Li
- State Key Laboratory of Freshwater Ecology and Biotechnology, Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Hubei Hongshan Laboratory, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China; College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Chengjie Liu
- State Key Laboratory of Freshwater Ecology and Biotechnology, Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Hubei Hongshan Laboratory, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China; College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Ru Zhang
- State Key Laboratory of Freshwater Ecology and Biotechnology, Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Hubei Hongshan Laboratory, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China; College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Yi Li
- State Key Laboratory of Freshwater Ecology and Biotechnology, Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Hubei Hongshan Laboratory, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China; College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Ding Ye
- State Key Laboratory of Freshwater Ecology and Biotechnology, Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Hubei Hongshan Laboratory, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China; College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Houpeng Wang
- State Key Laboratory of Freshwater Ecology and Biotechnology, Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Hubei Hongshan Laboratory, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China
| | - Mudan He
- State Key Laboratory of Freshwater Ecology and Biotechnology, Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Hubei Hongshan Laboratory, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China; College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Yonghua Sun
- State Key Laboratory of Freshwater Ecology and Biotechnology, Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Hubei Hongshan Laboratory, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China; College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing, China; The Innovation Academy of Seed Design, Chinese Academy of Sciences, Wuhan, China.
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15
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Zhang H, Ma X, Liu W, Wang Z, Zhang Z, Chen G, Zhang Y, Wang T, Yu T, Zhang Y. Causal relationship between serum metabolites and juvenile idiopathic arthritis: a mendelian randomization study. Pediatr Rheumatol Online J 2024; 22:51. [PMID: 38724970 PMCID: PMC11080266 DOI: 10.1186/s12969-024-00986-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Accepted: 04/25/2024] [Indexed: 05/13/2024] Open
Abstract
BACKGROUND Juvenile Idiopathic Arthritis (JIA) is a condition that occurs when individuals under the age of 16 develop arthritis that lasts for more than six weeks, and the cause is unknown. The development of JIA may be linked to serum metabolites. Nevertheless, the association between JIA pathogenesis and serum metabolites is unclear, and there are discrepancies in the findings across studies. METHODS In this research, the association between JIA in humans and 486 serum metabolites was assessed using genetic variation data and genome-wide association study. The identification of causal relationships was accomplished through the application of univariate Mendelian randomization (MR) analysis. Various statistical methods, including inverse variance weighted and MR-Egger, were applied to achieve this objective. To ensure that the findings from the MR analysis were trustworthy, a number of assessments were carried out. To ensure the accuracy of the obtained results, a range of techniques were utilised including the Cochran Q test, examination of the MR-Egger intercept, implementation of the leave-one-out strategy, and regression analysis of linkage disequilibrium scores. In order to identify the specific metabolic pathways associated with JIA, our primary objective was to perform pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes. RESULTS Two-sample summary data MR analyses and sensitivity analyses showed that five metabolites were significantly causally associated with JIA, including two risk factors-kynurenine (odds ratio [OR]: 16.39, 95% confidence interval [CI]: 2.07-129.63, p = 5.11 × 10- 6) and linolenate (OR: 16.48, 95% CI: 1.32-206.22, p = 0.030)-and three protective factors-3-dehydrocarnitine (OR: 0.32, 95% CI: 0.14-0.72, p = 0.007), levulinate (4-oxovalerate) (OR: 0.40, 95% CI: 0.20-0.80, p = 0.010), and X-14,208 (phenylalanylserine) (OR: 0.68, 95% CI: 0.51-0.92, p = 0.010). Furthermore, seven metabolic pathways, including α-linolenic acid metabolism and pantothenate and CoA biosynthesis, are potentially associated with the onset and progression of JIA. CONCLUSION Five serum metabolites, including kynurenine and 3-dehydrocarnitine, may be causally associated with JIA. These results provide a theoretical framework for developing effective JIA prevention and screening strategies.
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Affiliation(s)
- Han Zhang
- Department of Orthopedics, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xiao Ma
- Department of Orthopedics, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Wanlu Liu
- Shanxian Central Hospital, Heze, Shandong Province, China
| | - Ze Wang
- Department of Neurology, Qingdao Haici Hospital, Qingdao, China
| | - Zian Zhang
- Department of Orthopedics, Affiliated Hospital of Qingdao University, Qingdao, China
| | - GuanHong Chen
- Shanxian Central Hospital, Heze, Shandong Province, China
| | - Yingze Zhang
- Department of Orthopedics, Affiliated Hospital of Qingdao University, Qingdao, China
- Department of Orthopedics, The Third Hospital of Hebei Medical University, Shijiazhuang, China
| | - Tianrui Wang
- Department of Orthopedics, Affiliated Hospital of Qingdao University, Qingdao, China.
| | - Tengbo Yu
- Qingdao Municipal Hospital, Qingdao, China.
| | - Yongtao Zhang
- Department of Orthopedics, Affiliated Hospital of Qingdao University, Qingdao, China.
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16
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Ghooray DT, Xu M, Shi H, McClain CJ, Song M. Hepatocyte-Specific Fads1 Overexpression Attenuates Western Diet-Induced Metabolic Phenotypes in a Rat Model. Int J Mol Sci 2024; 25:4836. [PMID: 38732052 PMCID: PMC11084797 DOI: 10.3390/ijms25094836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 04/01/2024] [Accepted: 04/25/2024] [Indexed: 05/13/2024] Open
Abstract
Fatty acid desaturase 1 (FADS1) is a rate-limiting enzyme in long-chain polyunsaturated fatty acid (LCPUFA) synthesis. Reduced activity of FADS1 was observed in metabolic dysfunction-associated steatotic liver disease (MASLD). The aim of this study was to determine whether adeno-associated virus serotype 8 (AAV8) mediated hepatocyte-specific overexpression of Fads1 (AAV8-Fads1) attenuates western diet-induced metabolic phenotypes in a rat model. Male weanling Sprague-Dawley rats were fed with a chow diet, or low-fat high-fructose (LFHFr) or high-fat high-fructose diet (HFHFr) ad libitum for 8 weeks. Metabolic phenotypes were evaluated at the endpoint. AAV8-Fads1 injection restored hepatic FADS1 protein levels in both LFHFr and HFHFr-fed rats. While AAV8-Fads1 injection led to improved glucose tolerance and insulin signaling in LFHFr-fed rats, it significantly reduced plasma triglyceride (by ~50%) and hepatic cholesterol levels (by ~25%) in HFHFr-fed rats. Hepatic lipidomics analysis showed that FADS1 activity was rescued by AAV8-FADS1 in HFHFr-fed rats, as shown by the restored arachidonic acid (AA)/dihomo-γ-linolenic acid (DGLA) ratio, and that was associated with reduced monounsaturated fatty acid (MUFA). Our data suggest that the beneficial role of AAV8-Fads1 is likely mediated by the inhibition of fatty acid re-esterification. FADS1 is a promising therapeutic target for MASLD in a diet-dependent manner.
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Affiliation(s)
- Dushan T. Ghooray
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202, USA; (D.T.G.); (M.X.); (C.J.M.)
| | - Manman Xu
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202, USA; (D.T.G.); (M.X.); (C.J.M.)
| | - Hongxue Shi
- Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA;
- Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA
| | - Craig J. McClain
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202, USA; (D.T.G.); (M.X.); (C.J.M.)
- Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA;
- Hepatobiology & Toxicology Center, University of Louisville School of Medicine, Louisville, KY 40202, USA
- Alcohol Research Center, University of Louisville School of Medicine, Louisville, KY 40202, USA
- Robley Rex Veterans Affairs Medical Center, Louisville, KY 40206, USA
| | - Ming Song
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202, USA; (D.T.G.); (M.X.); (C.J.M.)
- Hepatobiology & Toxicology Center, University of Louisville School of Medicine, Louisville, KY 40202, USA
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Wang C, Fu RJ, Xu DQ, Zuo Q, Liu JP, Tang YP. A study integrated metabolomics and network pharmacology to investigate the effects of Shicao in alleviating acute liver injury. JOURNAL OF ETHNOPHARMACOLOGY 2024; 319:117369. [PMID: 38380571 DOI: 10.1016/j.jep.2023.117369] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 10/27/2023] [Accepted: 10/27/2023] [Indexed: 02/22/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Shicao is the aerial part of Achillea alpina L., a common herb found mainly in Europe, Asia, and North America. Traditional Chinese medicine has a history of thousands of years and is widely used to treat various diseases. AIM OF STUDY To explore the hepatoprotective effects of Shicao on CCl4-induced acute liver injury. METHODS A rat model of acute liver injury was established and liver function indices were assessed to evaluate the protective effect of Shicao on the liver. Untargeted metabolomics of the serum and liver tissues was conducted using UPLC-Q-TOF/MS to identify differential metabolites related to acute liver injury. A network of metabolite-reaction-enzyme-gene constituents was constructed using network pharmacology. Hub targets and key components of the effect of Shicao on acute liver injury were screened from the network. RESULTS Compared to the model group, Shicao improved the degree of liver damage through the assessment of the liver index, ALT and AST levels, and hepatic pathology slices, demonstrating its hepatoprotective effect against acute liver injury in rats. 10 and 38 differential metabolites involved in acute liver injury were identified in serum and liver tissues, respectively. Most of these were regulated or restored following treatment with Shicao, which mainly consisted of bile acids, lipids, and nucleotides such as taurocholic acid, LysoPC (17:0), and adenosine diphosphate ribose. Through the network of metabolite-reaction-enzyme-gene-constituents, 10 key components and 5 hub genes, along with 7 crucial differential metabolites, were mainly involved in glycerophospholipid metabolism, purine metabolism, biosynthesis of unsaturated fatty acids, and primary bile acid biosynthesis, which may play important roles in the prevention of acute liver injury by Shicao. CONCLUSION This study revealed that Shicao had protective effects against CCl4-induced liver injury in rats. It was speculated that the ingredients of Shicao might be closely related to the hub targets, thereby regulating the levels of key metabolites, affecting inflammatory response and oxidative stress and attenuate the liver injury consequently. This study provides a basis for further investigation of its therapeutic potential and the mechanism of action.
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Affiliation(s)
- Chao Wang
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi University of Chinese Medicine, Xi'an, 712046, Shaanxi Province, China
| | - Rui-Jia Fu
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi University of Chinese Medicine, Xi'an, 712046, Shaanxi Province, China.
| | - Ding-Qiao Xu
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi University of Chinese Medicine, Xi'an, 712046, Shaanxi Province, China
| | - Qian Zuo
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi University of Chinese Medicine, Xi'an, 712046, Shaanxi Province, China
| | - Ji-Ping Liu
- Key Laboratory of Pharmacodynamic Mechanism and Material Basis of Traditional Chinese Medicine, Shaanxi University of Chinese Medicine, Xi'an, 712046, Shaanxi Province, China
| | - Yu-Ping Tang
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi University of Chinese Medicine, Xi'an, 712046, Shaanxi Province, China.
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Wang K, Shi JH, Gao J, Sun Y, Wang Z, Shi X, Guo W, Jin Y, Zhang S. Arachidonic acid metabolism CYP450 pathway is deregulated in hepatocellular carcinoma and associated with microvascular invasion. Cell Biol Int 2024; 48:31-45. [PMID: 37655528 DOI: 10.1002/cbin.12086] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 07/08/2023] [Accepted: 08/21/2023] [Indexed: 09/02/2023]
Abstract
Arachidonic acid metabolism plays a crucial role in the development and progression of inflammatory and metabolic liver diseases. However, its role in hepatocellular carcinoma (HCC) remains unclear. In this study, we investigated the expression of key genes involved in the arachidonic acid metabolism pathway in HCC using a combination of bioinformatics, proteomics and immunohistochemistry analyses. Through a comprehensive analysis of publicly available datasets, clinical HCC tissues, and tissue microarrays, we compared the expression of hepatic arachidonic acid metabolic genes. We observed significant downregulation of cytochrome P450 (CYP450) pathway genes at both the messenger RNA and protein levels in HCC tissues compared to normal liver tissues. Furthermore, we observed a strong correlation between the deregulation of the arachidonic acid metabolism CYP450 pathway and the pathological features and prognosis of HCC. Specifically, the expression of CYP2C8/9/18/19 was significantly correlated with pathological grade (r = -.484, p < .0001), vascular invasion (r = -.402, p < .0001), aspartate transaminase (r = -.246, p = .025), gamma-glutamyl transpeptidase (r = -.252, p = .022), alkaline phosphatase (r = -.342, p = .002), alpha-fetoprotein (r = -.311, p = .004) and carbohydrate antigen 19-9 (r = -.227, p = .047). Moreover, we discovered a significant association between CYP450 pathway activity and vascular invasion in HCC. Collectively, these data indicate that arachidonic acid CYP450 metabolic pathway deregulation is implicated in HCC progression and may be a potential predictive factor for early recurrence in patients with HCC.
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Affiliation(s)
- Kai Wang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Diagnosis and Treatment League for Hepatopathy Henan Research Centre for Organ Transplantation, Zhengzhou, China
- Open and Key Laboratory for Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou, China
- Zhengzhou Key Laboratory for Hepatobiliary and Pancreatic Diseases and Organ Transplantation, Zhengzhou, China
| | - Ji-Hua Shi
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Diagnosis and Treatment League for Hepatopathy Henan Research Centre for Organ Transplantation, Zhengzhou, China
- Open and Key Laboratory for Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou, China
- Zhengzhou Key Laboratory for Hepatobiliary and Pancreatic Diseases and Organ Transplantation, Zhengzhou, China
| | - Jie Gao
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Diagnosis and Treatment League for Hepatopathy Henan Research Centre for Organ Transplantation, Zhengzhou, China
- Open and Key Laboratory for Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou, China
- Zhengzhou Key Laboratory for Hepatobiliary and Pancreatic Diseases and Organ Transplantation, Zhengzhou, China
| | - Yaohui Sun
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Diagnosis and Treatment League for Hepatopathy Henan Research Centre for Organ Transplantation, Zhengzhou, China
- Open and Key Laboratory for Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou, China
- Zhengzhou Key Laboratory for Hepatobiliary and Pancreatic Diseases and Organ Transplantation, Zhengzhou, China
| | - Zhihui Wang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Diagnosis and Treatment League for Hepatopathy Henan Research Centre for Organ Transplantation, Zhengzhou, China
- Open and Key Laboratory for Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou, China
- Zhengzhou Key Laboratory for Hepatobiliary and Pancreatic Diseases and Organ Transplantation, Zhengzhou, China
| | - Xiaoyi Shi
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Diagnosis and Treatment League for Hepatopathy Henan Research Centre for Organ Transplantation, Zhengzhou, China
- Open and Key Laboratory for Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou, China
- Zhengzhou Key Laboratory for Hepatobiliary and Pancreatic Diseases and Organ Transplantation, Zhengzhou, China
| | - Wenzhi Guo
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Diagnosis and Treatment League for Hepatopathy Henan Research Centre for Organ Transplantation, Zhengzhou, China
- Open and Key Laboratory for Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou, China
- Zhengzhou Key Laboratory for Hepatobiliary and Pancreatic Diseases and Organ Transplantation, Zhengzhou, China
| | - Yang Jin
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Shuijun Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Diagnosis and Treatment League for Hepatopathy Henan Research Centre for Organ Transplantation, Zhengzhou, China
- Open and Key Laboratory for Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou, China
- Zhengzhou Key Laboratory for Hepatobiliary and Pancreatic Diseases and Organ Transplantation, Zhengzhou, China
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Han C, Li Z, Liu R, Zhao Z, Wang Y, Zuo X, Zhang Y, Geng Z, Huang H, Pan X, Li W. Lonicerae flos polysaccharides improve nonalcoholic fatty liver disease by activating the adenosine 5'-monophosphate-activated protein kinase pathway and reshaping gut microbiota. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2023; 103:7721-7738. [PMID: 37439182 DOI: 10.1002/jsfa.12854] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Revised: 07/09/2023] [Accepted: 07/13/2023] [Indexed: 07/14/2023]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver cirrhosis and cancer. Lonicerae flos polysaccharides (LPs) have been shown to be effective in treating metabolic diseases; however, the therapeutic effects and underlying molecular mechanisms of LPs in NAFLD remain unclear. PURPOSE The objective of this study was to investigate the morphological characterization of Lonicerae flos polysaccharides (LPs) and the mechanism of LPs in relieving NAFLD. METHODS The morphology of LPs was observed using atomic force microscopy (AFM), X-ray diffraction (XRD), thermal weight (TG), and thermal weight derivative (DTG); NAFLD mice were treated with LPs at the same time as they were induced with a Western diet, and then the indexes related to glycolipid metabolism, fibrosis, inflammation, and autophagy in the serum and liver of the mice were detected. RESULTS The atomic force microscope analysis results indicated that the LPs displayed sugar-chain aggregates, exhibited an amorphous structure, and were relatively stable in thermal cracking at 150 °C. It was also found that LPs exerted therapeutic effects in NAFLD. The LPs prevented high-fat and -cholesterol diet-induced NAFLD progression by regulating glucose metabolism dysregulation, insulin resistance, lipid accumulation, inflammation, fibrosis, and autophagy. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) inhibitor compound C abrogated LP-induced hepatoprotection in mice with NAFLD. The LPs further treated NAFLD by reshaping the structure of the gut microbiota, in which Desulfovibrio bacteria plays a key roles. CONCLUSION Lonicerae flos polysaccharides exert protective effects against NAFLD in mice by improving the structure of the intestinal flora and activating the AMPK signaling pathway. © 2023 Society of Chemical Industry.
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Affiliation(s)
- Chao Han
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Zongshuo Li
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Ruiying Liu
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Zihan Zhao
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Yu Wang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Xuli Zuo
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Yushi Zhang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Zeyu Geng
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Houyu Huang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Xiuzhen Pan
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Weidong Li
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
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Machado M, Sousa S, Rodriguez-Alcalá LM, Gomes AM, Pintado M. Anti-obesity potential of a yogurt functionalized with a CLNA-rich pomegranate oil. Food Res Int 2023; 173:113364. [PMID: 37803704 DOI: 10.1016/j.foodres.2023.113364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Revised: 08/03/2023] [Accepted: 08/05/2023] [Indexed: 10/08/2023]
Abstract
Pomegranate oil is rich in conjugated linolenic acids, compounds which have attracted attention due to their potential applicability in obesity management as they are capable of modulating leptin and adiponectin secretion and regulate fatty acids storage and glucose metabolism. Among the possible bioactive foodstuffs capable of delivering these bioactive compounds yogurts have shown potential. Thus, the purpose of this work was to develop functional yogurts through the addition of pomegranate oil either in its free or encapsulated (used as a protective strategy against oxidation and gastrointestinal tract passage) forms. To that end, the pomegranate oil (free and encapsulated) was incorporated in yogurt and the functional yogurt capacity to modulate hepatic lipid accumulation, adipocyte metabolism (in terms of lipolysis, and adipokines secretion) and immune response was evaluated. The results obtained showed that the pomegranate oil's incorporation led to an improvement in the yogurts' nutritional values, with a reduction in its atherogenic and thrombogenic indexes (more than 78% for atherogenic and 76% for thrombogenic index) and an enhancement of its hypocholesterolemic/hypercholesterolemic ratio (more than 62%) when compared to the control yogurt. Furthermore, data also showed for the first time how these functional yogurts promoted modulation of metabolic processes post GIT as they were capable of reducing by 40% triglycerides accumulation in steatosis-induced Hep G2 cells and by 30 % in differentiated adipocytes. Moreover, samples also showed a capacity to modulate the leptin and adiponectin secretion (56 % of increase in adiponectin) and reduce the IL-6 secretion (ca 44%) and TNF-α (ca 12%) in LPS-stimulated cells. Thus, the CLNA-rich yogurt here developed showed potential as a viable nutraceutical alternative for obesity management.
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Affiliation(s)
- Manuela Machado
- Universidade Católica Portuguesa, CBQF Centro de Biotecnologia e Química Fina-Laboratório Associado, Escola Superior de Biotecnologia, Rua Diogo Botelho 1327, 4169-005 Porto, Portugal
| | - Sérgio Sousa
- Universidade Católica Portuguesa, CBQF Centro de Biotecnologia e Química Fina-Laboratório Associado, Escola Superior de Biotecnologia, Rua Diogo Botelho 1327, 4169-005 Porto, Portugal
| | - Luís M Rodriguez-Alcalá
- Universidade Católica Portuguesa, CBQF Centro de Biotecnologia e Química Fina-Laboratório Associado, Escola Superior de Biotecnologia, Rua Diogo Botelho 1327, 4169-005 Porto, Portugal
| | - Ana Maria Gomes
- Universidade Católica Portuguesa, CBQF Centro de Biotecnologia e Química Fina-Laboratório Associado, Escola Superior de Biotecnologia, Rua Diogo Botelho 1327, 4169-005 Porto, Portugal
| | - Manuela Pintado
- Universidade Católica Portuguesa, CBQF Centro de Biotecnologia e Química Fina-Laboratório Associado, Escola Superior de Biotecnologia, Rua Diogo Botelho 1327, 4169-005 Porto, Portugal.
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Yin K, Wang D, Zhang Y, Lu H, Wang Y, Xing M. Dose-effect of polystyrene microplastics on digestive toxicity in chickens (Gallus gallus): Multi-omics reveals critical role of gut-liver axis. J Adv Res 2023; 52:3-18. [PMID: 36334886 PMCID: PMC10555772 DOI: 10.1016/j.jare.2022.10.015] [Citation(s) in RCA: 63] [Impact Index Per Article: 31.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 09/19/2022] [Accepted: 10/28/2022] [Indexed: 11/11/2022] Open
Abstract
INTRODUCTION Microplastic pollution seriously threatens the health and safety of humans and wildlife. Avian is one of the main species endangered by microplastics. However, the damage mechanism of microplastics to the digestive system of avian is not clear. OBJECTIVES The gut-liver axis is a bidirectional channel that regulates the exchange of information between the gut and the liver and is also a key target for tissue damage caused by pollutants. This study aimed to elucidate the digestive toxicity of microplastics in avian and the key role of the gut-liver axis in it. METHODS We constructed an exposure model for microplastics in environmental concentrations and toxicological concentrations in chickens and reveal the digestive toxicity of polystyrene microplastics (PS-MPs) in avian by 16S rRNA, transcriptomics and metabolomics. RESULTS PS-MPs changed the death mode from apoptosis to necrosis and pyroptosis by upregulating Caspase 8, disrupting the intestinal vascular barrier, disturbing the intestinal flora and promoting the accumulation of lipopolysaccharide. Harmful flora and metabolites were translocated to the liver through the liver-gut axis, eliciting hepatic immune responses and promoting hepatic lipid metabolism disorders and apoptosis. Liver injury involves multiple molecular effects of mitochondrial dynamics disturbance, oxidative stress, endoplasmic reticulum stress, and cell cycle disturbance. Furthermore, metabolomics suggested that caffeine and melanin metabolites may be potential natural resistance substances for microplastics. CONCLUSION Taken together, our data demonstrate the digestive damage of PS-MPs in avian, revealing a critical role of the liver-gut axis in it. This will provide a reference for protecting the safety of avian populations.
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Affiliation(s)
- Kai Yin
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin 150040, Heilongjiang, PR China
| | - Dongxu Wang
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin 150040, Heilongjiang, PR China
| | - Yue Zhang
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin 150040, Heilongjiang, PR China
| | - Hongmin Lu
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin 150040, Heilongjiang, PR China
| | - Yu Wang
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin 150040, Heilongjiang, PR China.
| | - Mingwei Xing
- College of Wildlife and Protected Area, Northeast Forestry University, Harbin 150040, Heilongjiang, PR China.
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Barroso LN, Salarini J, Leite NC, Villela-Nogueira CA, Dávalos A, Carmo MDGT, Ferreira Peres WA. Effect of fish oil supplementation on the concentration of miRNA-122, FGF-21 and liver fibrosis in patients with NAFLD: Study protocol for a randomized, double-blind and placebo-controlled clinical trial. Clin Nutr ESPEN 2023; 57:117-125. [PMID: 37739645 DOI: 10.1016/j.clnesp.2023.06.027] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 06/22/2023] [Accepted: 06/25/2023] [Indexed: 09/24/2023]
Abstract
BACKGROUND & AIMS To date, no specific drugs are available for non-alcoholic fatty liver disease (NAFLD), though the effect of fish oil supplementation on improving fibrosis in patients with NAFLD has been evaluated. N-3 polyunsaturated fatty acids (n-3 PUFA) may modulate the concentration of microRNAs (miRNAs) and fibroblast growth factor (FGF)-21, which have been identified as non-invasive markers of liver fibrosis. The present study aims to evaluate whether n-3 PUFA supplementation can modulate miRNA-122 and FGF-21 and improve liver fibrosis and steatosis, measured by transient hepatic elastography (THE), in individuals with NAFLD. METHODS A randomized, double-blind, placebo-controlled clinical trial will be conducted to evaluate the effect of 4 g/day supplementation of fish oil (2100 mg EPA and 924 mg DHA) in patients with NAFLD over a 6-month period. Fifty-two patients aged >19 years will be randomly assigned to either a placebo (olive oil) or treatment (fish oil) group. Anthropometric data, food intake, physical activity, body composition, resting energy expenditure (evaluated using indirect calorimetry), liver enzymes, platelets, lipids and glucose profile, inflammatory markers (such as C-reactive protein, neutrophil/lymphocyte, platelet/lymphocyte, and monocyte/lymphocyte ratios), miRNA-122 and FGF-21 concentration, and incorporation of fatty acids into the erythrocyte membrane (analyzed using gas chromatography) as well as the degree of liver fibrosis and steatosis assessed using THE (Fibroscan® Touch 502, Paris, France) and liver biomarkers Steato-Brazilian Longitudinal Study of Adult Health, Fatty Liver Index, NAFLD Fibrosis Score, Fibrosis-4 score, and FibroScan-AST score will be evaluated at the beginning and end of the treatment. Continuous variables with normal distribution will be compared between placebo and intervention groups using Student's T test for independent samples; continuous non-parametric variables will be compared using Dunn or Mann-Whitney test. Associations between categorical variables will be analyzed using the chi-square test, and within-group differences will be evaluated using the Wilcoxon signed-ranks test. The criterion for determining significance will be set at 5%. CONCLUSION The present study protocol will investigate the supplementation of EPA-rich fish oil as an alternative treatment for NAFLD and its feasibility in affecting the concentration of miRNA-122 and FGF-21 markers. Its findings will offer valuable contributions to the literature. REGISTRATION ReBEC number RBR-8dp876.
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Affiliation(s)
- Lygia N Barroso
- Josué de Castro Nutrition Institute, Federal University of Rio de Janeiro, Carlos Chagas Filho Avenue, 367/CCS - Block J2, University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil; School of (M)edicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Prof. Rodolpho Paulo Rocco Street, 255 - University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil
| | - Jessica Salarini
- Josué de Castro Nutrition Institute, Federal University of Rio de Janeiro, Carlos Chagas Filho Avenue, 367/CCS - Block J2, University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil; School of (M)edicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Prof. Rodolpho Paulo Rocco Street, 255 - University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil
| | - Nathalie Carvalho Leite
- School of (M)edicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Prof. Rodolpho Paulo Rocco Street, 255 - University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil
| | - Cristiane A Villela-Nogueira
- School of (M)edicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Prof. Rodolpho Paulo Rocco Street, 255 - University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil
| | - Alberto Dávalos
- Laboratory of Epigenetics of Lipid Metabolism, Madrid Institute for Advanced Studies (IMDEA), Madrid, Spain
| | - Maria das Graças Tavares Carmo
- Josué de Castro Nutrition Institute, Federal University of Rio de Janeiro, Carlos Chagas Filho Avenue, 367/CCS - Block J2, University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil
| | - Wilza Arantes Ferreira Peres
- Josué de Castro Nutrition Institute, Federal University of Rio de Janeiro, Carlos Chagas Filho Avenue, 367/CCS - Block J2, University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil.
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23
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Liu Z, Huang H, Zeng Y, Chen Y, Xu C. Association between ultra-processed foods consumption and risk of non-alcoholic fatty liver disease: a population-based analysis of NHANES 2011-2018. Br J Nutr 2023; 130:996-1004. [PMID: 36522692 DOI: 10.1017/s0007114522003956] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
An increasing number of studies have evaluated the association between ultra-processed foods (UPF) consumption and metabolic disorders. However, the association between UPF intake and non-alcoholic fatty liver disease (NAFLD) remains unclear. In this study, we analysed data from 6545 participants who were recruited in National Health and Nutrition Examination Surveys 2011-2018. UPF were defined in light of the NOVA food classification system and divided into quartiles based on its proportion of total weight intake. Complex logistic regression models were used to assess the association between UPF and NAFLD. Mediation analyses were conducted to reveal underlying mediators. We found that NAFLD patients consumed more UPF than controls (925·92 ± 18·08 v. 812·70 ± 14·32 g/d, P < 0·001). Dietary intake of UPF (% weight) was negatively related to the Healthy Eating Index-2015 score (Spearman r = -0·32, P < 0·001). In the multivariable model, the highest quartile compared with the lowest, the OR (95 % CI) were 1·83 (1·33, 2·53) for NAFLD (OR per 10 % increment: 1·15; 95 % CI: 1·09, 1·22; P for trend < 0·001) and 1·52 (1·12, 2·07) for insulin resistance (OR per 10 % increment: 1·11; 95 % CI: 1·05, 1·18; P for trend = 0·002). Mediation analyses revealed that poor diet quality, high saturated fat and refined grain intake partly mediated the association between UPF and NAFLD. In conclusion, high UPF intake was associated with an increased risk of NAFLD in US adults. Further prospective studies are needed to verify these findings.
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Affiliation(s)
- Zhening Liu
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou310003, People's Republic of China
| | - Hangkai Huang
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou310003, People's Republic of China
| | - Yan Zeng
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou310003, People's Republic of China
| | - Yishu Chen
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou310003, People's Republic of China
| | - Chengfu Xu
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou310003, People's Republic of China
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Moghtadaie A, Mahboobi H, Fatemizadeh S, Kamal MA. Emerging role of nanotechnology in treatment of non-alcoholic fatty liver disease (NAFLD). EXCLI JOURNAL 2023; 22:946-974. [PMID: 38023570 PMCID: PMC10630531 DOI: 10.17179/excli2023-6420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 08/29/2023] [Indexed: 12/01/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a prevailing health challenge that requires urgent innovative interventions. This review explores the role of nanotechnology as a promising potential in the treatment of NAFLD. It delineates the limitations of the current management strategies for NAFLD and highlights the new nanotechnology-based treatments including nanoemulsions, liposomes, micelles, polymeric nanoparticles, nanogels, inorganic nanoparticles, and zinc oxide nanoparticles. Despite the optimism surrounding the nanotechnological approach, the review underscores the need to address the limitations such as technical challenges, potential toxicity, and ethical considerations that impede the practical application of nanotechnology in NAFLD management. It advocates for collaborative efforts from researchers, clinicians, ethicists, and policymakers to achieve safe, effective, and equitable nanotechnology-based treatments for NAFLD. See also Figure 1(Fig. 1).
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Affiliation(s)
- Atie Moghtadaie
- Clinical Fellow in Gastroenterology and Hepatology, Digestive Disease Research Institute, Department of Gastroenterology and Hepatology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamidreza Mahboobi
- Clinical Fellow in Gastroenterology and Hepatology, Digestive Disease Research Institute, Department of Gastroenterology and Hepatology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Somayeh Fatemizadeh
- Department of Gastroenterology and Hepatology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Amjad Kamal
- Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, China
- King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
- Enzymoics, 7 Peterlee place, Hebersham, NSW 2770; Novel Global Community Educational Foundation, Australia
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25
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Dong Y, Wei Y, Wang L, Song K, Zhang C, Lu K, Rahimnejad S. Dietary n-3/n-6 polyunsaturated fatty acid ratio modulates growth performance in spotted seabass ( Lateolabrax maculatus) through regulating lipid metabolism, hepatic antioxidant capacity and intestinal health. ANIMAL NUTRITION (ZHONGGUO XU MU SHOU YI XUE HUI) 2023; 14:20-31. [PMID: 37234947 PMCID: PMC10208799 DOI: 10.1016/j.aninu.2023.04.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 01/12/2023] [Accepted: 04/04/2023] [Indexed: 05/28/2023]
Abstract
An 8-week feeding experiment was carried out to explore the effects of dietary n-3/n-6 polyunsaturated fatty acid (PUFA) ratio on growth performance, lipid metabolism, hepatic antioxidant status, and gut flora of spotted seabass (Lateolabrax maculatus). Six experimental diets were formulated to contain different levels of two purified oil sources including docosahexaenoic and eicosapentaenoic acids enriched oil (n-3) and linoleic acid-enriched oil (n-6) leading to n-3/n-6 PUFA ratios of 0.04, 0.35, 0.66, 1.35, 2.45 and 16.17. Each diet was fed to triplicate groups of juvenile L. maculatus (11.06 ± 0.20 g, 30 fish/tank). Final body weight (FBW), weight gain (WG), specific growth rates (SGR), protein efficiency ratio (PER) and feed utilization efficiency increased as n-3/n-6 PUFA ratio increased up to a certain level, and then decreased thereafter. Fish fed the diet with n-3/n-6 PUFA ratio of 0.66 exhibited the highest FBW, WG, SGR and PER and the lowest feed conversion ratio. Lower n-3/n-6 PUFA ratios induced up-regulated expression of lipid synthesis-related genes (fas, acc2 and srebp-1c) and down-regulated expression of lipolysis related genes (atgl, pparα, cpt-1 and aox). Higher expression of lipolysis-related genes (atgl, pparα and cpt-1) was recorded at moderate n-3/n-6 PUFA ratios (0.66 to 1.35). Moreover, inappropriate n-3/n-6 PUFA ratios triggered up-regulation of pro-inflammatory genes (il-6 and tnf-α) and down-regulation of anti-inflammatory genes (il-4 and il-10) in the intestine. The diet with n-3/n-6 PUFA ratio of 0.66 inhibited intestine inflammation, improved intestinal flora richness, increased the abundance of beneficial bacteria such as Lactobacillus, Alloprevotella and Ruminococcus, and reduced the abundance of harmful bacteria including Escherichia-Shigella and Enterococcus. In summary, it could be suggested that a dietary n-3/n-6 PUFA ratio of 0.66 can improve growth performance and feed utilization in L. maculatus, as is deemed to be mediated through regulation of lipid metabolism and intestinal flora.
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Affiliation(s)
- Yanzou Dong
- Key Laboratory of Healthy Mariculture for the East China Sea, Ministry of Agriculture and Rural Affairs, Fisheries College, Jimei University, Xiamen 361021, China
| | - Yu Wei
- Key Laboratory of Healthy Mariculture for the East China Sea, Ministry of Agriculture and Rural Affairs, Fisheries College, Jimei University, Xiamen 361021, China
| | - Ling Wang
- Key Laboratory of Healthy Mariculture for the East China Sea, Ministry of Agriculture and Rural Affairs, Fisheries College, Jimei University, Xiamen 361021, China
| | - Kai Song
- Key Laboratory of Healthy Mariculture for the East China Sea, Ministry of Agriculture and Rural Affairs, Fisheries College, Jimei University, Xiamen 361021, China
| | - Chunxiao Zhang
- Key Laboratory of Healthy Mariculture for the East China Sea, Ministry of Agriculture and Rural Affairs, Fisheries College, Jimei University, Xiamen 361021, China
| | - Kangle Lu
- Key Laboratory of Healthy Mariculture for the East China Sea, Ministry of Agriculture and Rural Affairs, Fisheries College, Jimei University, Xiamen 361021, China
| | - Samad Rahimnejad
- Faculty of Fisheries and Protection of Waters, University of South Bohemia in České Budějovice, South Bohemian Research Centre of Aquaculture and Biodiversity of Hydrocenoses, Vodňany, Zátiší 728, Vodňany 389 25, Czech Republic
- Fish Innate Immune System Group, Department of Cell Biology and Histology, Faculty of Biology, Regional Campus of International Excellence “Campus Mare Nostrum”, University of Murcia, Murcia 30100, Spain
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Liu X, Wang K, Wang L, Kong L, Hou S, Wan Y, Ma C, Chen J, Xing X, Xing C, Jiang Q, Zhao Q, Cui B, Huang Z, Li P. Hepatocyte leukotriene B4 receptor 1 promotes NAFLD development in obesity. Hepatology 2023; 78:562-577. [PMID: 35931467 DOI: 10.1002/hep.32708] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 08/01/2022] [Accepted: 08/02/2022] [Indexed: 01/04/2023]
Abstract
BACKGROUND AND AIMS NAFLD is the most prevalent chronic liver disease worldwide and has emerged as a serious public health issue with no approved treatment. The development of NAFLD is strongly associated with hepatic lipid content, and patients with NAFLD have significantly higher rates of hepatic de novo lipogenesis (DNL) than lean individuals. Leukotriene B4 (LTB4), a metabolite of arachidonic acid, is dramatically increased in obesity and plays important role in proinflammatory cytokine production and insulin resistance. But the role of liver LTB4/LTB4 receptor 1 (Ltb4r1) in lipid metabolism is unclear. APPROACH AND RESULTS Hepatocyte-specific knockout (HKO) of Ltb4r1 improved hepatic steatosis and systemic insulin resistance in both diet-induced and genetically induced obese mice. The mRNA level of key enzymes involved in DNL and fatty acid esterification decreased in Ltb4r1 HKO obese mice. LTB4/Ltb4r1 directly promoted lipogenesis in HepG2 cells and primary hepatocytes. Mechanically, LTB4/Ltb4r1 promoted lipogenesis by activating the cAMP-protein kinase A (PKA)-inositol-requiring enzyme 1α (IRE1α)-spliced X-box-binding protein 1 (XBP1s) axis in hepatocytes, which in turn promoted the expression of lipogenesis genes regulated by XBP1s. In addition, Ltb4r1 suppression through the Ltb4r1 inhibitor or lentivirus-short hairpin RNA delivery alleviated the fatty liver phenotype in obese mice. CONCLUSIONS LTB4/Ltb4r1 promotes hepatocyte lipogenesis directly by activating PKA-IRE1α-XBP1s to promote lipogenic gene expression. Inhibition of hepatocyte Ltb4r1 improved hepatic steatosis and insulin resistance. Ltb4r1 is a potential therapeutic target for NAFLD.
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Affiliation(s)
- Xingfeng Liu
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
- Diabetes Research Center of the Chinese Academy of Medical Sciences , Beijing , China
- CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis , Beijing , China
| | - Kai Wang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
- Diabetes Research Center of the Chinese Academy of Medical Sciences , Beijing , China
- CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis , Beijing , China
| | - Luhai Wang
- School of Pharmaceutical Sciences , Wenzhou Medical University , Wenzhou , Zhejiang , China
| | - Lijuan Kong
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
- Diabetes Research Center of the Chinese Academy of Medical Sciences , Beijing , China
- CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis , Beijing , China
| | - Shaocong Hou
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
- Diabetes Research Center of the Chinese Academy of Medical Sciences , Beijing , China
- CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis , Beijing , China
| | - Yanjun Wan
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
- Diabetes Research Center of the Chinese Academy of Medical Sciences , Beijing , China
- CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis , Beijing , China
| | - Chunxiao Ma
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
- Diabetes Research Center of the Chinese Academy of Medical Sciences , Beijing , China
- CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis , Beijing , China
| | - Jingwen Chen
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
- Diabetes Research Center of the Chinese Academy of Medical Sciences , Beijing , China
- CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis , Beijing , China
| | - Xiaowei Xing
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
- Diabetes Research Center of the Chinese Academy of Medical Sciences , Beijing , China
- CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis , Beijing , China
| | - Caiyi Xing
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
- Diabetes Research Center of the Chinese Academy of Medical Sciences , Beijing , China
- CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis , Beijing , China
| | - Qian Jiang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
- Diabetes Research Center of the Chinese Academy of Medical Sciences , Beijing , China
- CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis , Beijing , China
| | - Qijin Zhao
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
- Diabetes Research Center of the Chinese Academy of Medical Sciences , Beijing , China
- CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis , Beijing , China
| | - Bing Cui
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
| | - Zhifeng Huang
- School of Pharmaceutical Sciences , Wenzhou Medical University , Wenzhou , Zhejiang , China
| | - Pingping Li
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
- Diabetes Research Center of the Chinese Academy of Medical Sciences , Beijing , China
- CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis , Beijing , China
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Vell MS, Creasy KT, Scorletti E, Seeling KS, Hehl L, Rendel MD, Schneider KM, Schneider CV. Omega-3 intake is associated with liver disease protection. Front Public Health 2023; 11:1192099. [PMID: 37538264 PMCID: PMC10394692 DOI: 10.3389/fpubh.2023.1192099] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 07/04/2023] [Indexed: 08/05/2023] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease are among the most common liver diseases worldwide, and there are currently no Food and Drug Administration (FDA)-approved treatments. Recent studies have focused on lifestyle changes to prevent and treat NAFLD. Omega-3 supplementation is associated with improved outcomes in patients with chronic liver disease. However, it is unclear whether Omega-3 supplementation can prevent the development of liver disease, particularly in individuals at an increased (genetic) risk. Methods In this UK Biobank cohort study, we established a multivariate cox proportional hazards model for the risk of incident liver disease during an 11 year follow up time. We adjusted the model for diabetes, prevalent cardiovascular disorders, socioeconomic status, diet, alcohol consumption, physical activity, medication intake (insulin, biguanides, statins and aspirin), and baseline characteristics. Results Omega-3 supplementation reduced the risk of incident liver disease (HR = 0.716; 95% CI: 0.639, 0.802; p = 7.6 × 10-9). This protective association was particularly evident for alcoholic liver disease (HR = 0.559; 95% CI: 0.347, 0.833; p = 4.3 × 10-3), liver failure (HR = 0.548; 95% CI: 0.343, 0.875; p = 1.2 × 10-2), and non-alcoholic liver disease (HR = 0.784; 95% CI: 0.650, 0.944; p = 1.0 × 10-2). Interestingly, we were able to replicate the association with reduced risk of NAFLD in a subset with liver MRIs (HR = 0.846; 95% CI: 0.777, 0.921; p = 1.1 × 10-4). In particular, women benefited from Omega-3 supplementation as well as heterozygous allele carriers of the liver-damaging variant PNPLA3 rs738409. Conclusions Omega-3 supplementation may reduce the incidence of liver disease. Our study highlights the potential of personalized treatment strategies for individuals at risk of metabolic liver disease. Further evaluation in clinical trials is warranted before Omega-3 can be recommended for the prevention of liver disease.
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Affiliation(s)
- Mara Sophie Vell
- Department of Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
| | - Kate Townsend Creasy
- Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, PA, United States
| | - Eleonora Scorletti
- Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
| | - Katharina Sophie Seeling
- Department of Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
| | - Leonida Hehl
- Department of Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
| | - Miriam Daphne Rendel
- Department of Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
| | - Kai Markus Schneider
- Department of Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
| | - Carolin Victoria Schneider
- Department of Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
- Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
- The Institute for Translational Medicine and Therapeutics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
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Li Y, Wu S, Zhao X, Hao S, Li F, Wang Y, Liu B, Zhang D, Wang Y, Zhou H. Key events in cancer: Dysregulation of SREBPs. Front Pharmacol 2023; 14:1130747. [PMID: 36969840 PMCID: PMC10030587 DOI: 10.3389/fphar.2023.1130747] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Accepted: 02/22/2023] [Indexed: 03/11/2023] Open
Abstract
Lipid metabolism reprogramming is an important hallmark of tumor progression. Cancer cells require high levels of lipid synthesis and uptake not only to support their continued replication, invasion, metastasis, and survival but also to participate in the formation of biological membranes and signaling molecules. Sterol regulatory element binding proteins (SREBPs) are core transcription factors that control lipid metabolism and the expression of important genes for lipid synthesis and uptake. A growing number of studies have shown that SREBPs are significantly upregulated in human cancers and serve as intermediaries providing a mechanistic link between lipid metabolism reprogramming and malignancy. Different subcellular localizations, including endoplasmic reticulum, Golgi, and nucleus, play an indispensable role in regulating the cleavage maturation and activity of SREBPs. In this review, we focus on the relationship between aberrant regulation of SREBPs activity in three organelles and tumor progression. Because blocking the regulation of lipid synthesis by SREBPs has gradually become an important part of tumor therapy, this review also summarizes and analyzes several current mainstream strategies.
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Affiliation(s)
- Yunkuo Li
- Department of Urology, The First Hospital of Jilin University, Changchun, China
| | - Shouwang Wu
- Department of Urology, The First Hospital of Jilin University, Changchun, China
| | - Xiaodong Zhao
- Department of Urology, The First Hospital of Jilin University, Changchun, China
| | - Shiming Hao
- Department of Urology, The First Hospital of Jilin University, Changchun, China
| | - Faping Li
- Department of Urology, The First Hospital of Jilin University, Changchun, China
| | - Yuxiong Wang
- Department of Urology, The First Hospital of Jilin University, Changchun, China
| | - Bin Liu
- Department of Urology, The First Hospital of Jilin University, Changchun, China
| | - Difei Zhang
- Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, China
| | - Yishu Wang
- Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, China
- *Correspondence: Yishu Wang, Honglan Zhou,
| | - Honglan Zhou
- Department of Urology, The First Hospital of Jilin University, Changchun, China
- *Correspondence: Yishu Wang, Honglan Zhou,
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Raith M, Nguyen N, Kauffman SJ, Kang N, Mays J, Dalhaimer P. Obesity and inflammation influence pharmacokinetic profiles of PEG-based nanoparticles. J Control Release 2023; 355:434-445. [PMID: 36758834 PMCID: PMC10006354 DOI: 10.1016/j.jconrel.2023.02.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Revised: 02/02/2023] [Accepted: 02/03/2023] [Indexed: 02/11/2023]
Abstract
Most patients that will be treated with soft nanoparticles (NPs) will be obese. Yet, NP testing, which begins with pharmacokinetic (PK) and toxicity studies, is carried out almost exclusively in lean rodents having healthy livers and low inflammation. To address this knowledge gap, we determined the PK and toxicity of tail-vein-injected, PEG-based cylindrical nanoparticles (CNPs) and PEGylated liposomes (PLs) as a function of obesity, liver health, and inflammation in leptin-deficient ob/ob and wild-type C57BL/6 J mice. CNPs localized faster to obese livers than to healthy livers within 24 h of injection. PLs localized faster to obese livers than to healthy livers but only 30 min post-injection. Afterwards PL localization to lean livers was higher than localization to obese livers. Overall, PL liver signal peaked ∼6 h post-injection in lean mice, ∼24 h post-injection in heavy mice, and ∼ 48 h post-injection in obese mice. CNPs and PLs were non-toxic to mouse livers as assessed by histology; they reduced many cytokine and chemokine levels that were elevated by obesity. Liver macrophage depletion reduced CNP and PL liver localization as expected; liver sinusoidal endothelial cell (LSEC) depletion reduced PL liver localization but surprisingly increased CNP liver localization. The intensity of RAW264.7 macrophages was higher after CNP incubations than with PL incubations; conversely, the intensity of LSECs was higher after PL incubations than with CNP incubations. This shows the potential for key differences in NP-liver interactions. Triggering inflammation by administering lipopolysaccharide (LPS) to mice increased CNP liver localization but decreased PL liver localization. The results show that obesity and inflammation in a mouse model and in vitro affect soft PEG-based NP interaction with macrophages and LSECs, but also that these NPs can reduce pro-inflammatory pathways increased by obesity.
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Affiliation(s)
- Mitch Raith
- Department of Chemical and Biomolecular Engineering, Knoxville, TN 37996, United States of America
| | - Nicole Nguyen
- Department of Biochemistry, Cellular, and Molecular Biology, Knoxville, TN 37996, United States of America
| | - Sarah J Kauffman
- Department of Microbiology, Knoxville, TN 37996, United States of America
| | - Namgoo Kang
- Department of Chemistry, University of Tennessee, Knoxville, TN 37996, United States of America
| | - Jimmy Mays
- Department of Chemistry, University of Tennessee, Knoxville, TN 37996, United States of America
| | - Paul Dalhaimer
- Department of Chemical and Biomolecular Engineering, Knoxville, TN 37996, United States of America; Department of Biochemistry, Cellular, and Molecular Biology, Knoxville, TN 37996, United States of America.
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30
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Lopez-Pentecost M, Hallmark B, Thomson CA, Chilton F, Garcia DO. Association between Dietary Fatty Acid Intake and Liver Steatosis and Fibrosis in a Sample of Mexican-Origin Hispanic Adults with Overweight or Obesity. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:3103. [PMID: 36833798 PMCID: PMC9960945 DOI: 10.3390/ijerph20043103] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 02/07/2023] [Accepted: 02/09/2023] [Indexed: 06/18/2023]
Abstract
Rates of non-alcoholic fatty liver disease (NAFLD) vary dramatically among Hispanic subpopulations, with Mexican-origin (MO) Hispanics experiencing a disproportionate burden. This study examined dietary fatty acid (FA) intake among overweight and obese MO Hispanic adults in the United States (US) and evaluated its association with liver steatosis and fibrosis. Participants (N = 285, MO Hispanic adults) completed 24-h dietary recalls to assess dietary FA exposure. Liver steatosis and fibrosis were estimated using transient elastography (FibroScan®). Multiple regression analysis tested relationships between FA intakes and liver steatosis or fibrosis, adjusting for age, sex, body mass index (BMI) and total energy. A total of 51% (n = 145) of participants were suspected to have NAFLD and 20% self-reported a type 2 diabetes diagnosis. No significant association was observed between Linoleic Acid and α-Linolenic Acid (LA:ALA) ratio, or omega-6 to omega-3 (n-6:n-3) ratio and liver steatosis. However, a one-point increase in the LA:ALA ratio resulted in a 1.01% increase in the liver fibrosis scores (95% CI: [1.00, 1.03]; p = 0.03), and a one-point increase in the n-6:n-3 ratio resulted in a 1.02% increase in liver fibrosis score (95% CI: [1.01, 1.03]; p = 0.01). Further research is needed to determine if modulation of FA intake could reduce NAFLD risk in this high-risk population.
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Affiliation(s)
- Melissa Lopez-Pentecost
- Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Brian Hallmark
- The BIO5 Institute, University of Arizona, Tucson, AZ 85721, USA
| | - Cynthia A. Thomson
- Department of Health Promotion Sciences Tucson, University of Arizona, Tucson, AZ 85721, USA
| | - Floyd Chilton
- The BIO5 Institute, University of Arizona, Tucson, AZ 85721, USA
- Department of Nutritional Sciences, University of Arizona, Tucson, AZ 85721, USA
| | - David O. Garcia
- Department of Health Promotion Sciences Tucson, University of Arizona, Tucson, AZ 85721, USA
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Monirujjaman M, Renani LB, Isesele P, Dunichand-Hoedl AR, Mazurak VC. Increased Expression of Hepatic Stearoyl-CoA Desaturase (SCD)-1 and Depletion of Eicosapentaenoic Acid (EPA) Content following Cytotoxic Cancer Therapy Are Reversed by Dietary Fish Oil. Int J Mol Sci 2023; 24:ijms24043547. [PMID: 36834959 PMCID: PMC9962117 DOI: 10.3390/ijms24043547] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 02/03/2023] [Accepted: 02/07/2023] [Indexed: 02/12/2023] Open
Abstract
Cancer treatment evokes impediments to liver metabolism that culminate in fatty liver. This study determined hepatic fatty acid composition and expression of genes and mediators involved in lipid metabolism following chemotherapy treatment. Female rats bearing the Ward colon tumor were administered Irinotecan (CPT-11) +5-fluorouracil (5-FU) and maintained on a control diet or a diet containing eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) (2.3 g/100 g fish oil). Healthy animals provided with a control diet served as a reference group. Livers were collected one week after chemotherapy. Triacylglycerol (TG), phospholipid (PL), ten lipid metabolism genes, leptin, and IL-4 were measured. Chemotherapy increased TG content and reduced EPA content in the liver. Expression of SCD1 was upregulated by chemotherapy, while dietary fish oil downregulated its expression. Dietary fish oil down-regulated expression of the fatty acid synthesis gene FASN, while restoring the long chain fatty acid converting genes FADS2 and ELOVL2, and genes involved in mitochondrial β-oxidation (CPT1α) and lipid transport (MTTP1), to values similar to reference animals. Neither leptin nor IL-4 were affected by chemotherapy or diet. Depletion of EPA is associated with pathways evoking enhanced TG accumulation in the liver. Restoring EPA through diet may pose a dietary strategy to attenuate chemotherapy-associated impediments in liver fatty acid metabolism.
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Musazadeh V, Karimi A, Malekahmadi M, Ahrabi SS, Dehghan P. Omega-3 polyunsaturated fatty acids in the treatment of non-alcoholic fatty liver disease: An umbrella systematic review and meta-analysis. Clin Exp Pharmacol Physiol 2023; 50:327-334. [PMID: 36692292 DOI: 10.1111/1440-1681.13750] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 12/17/2022] [Accepted: 01/10/2023] [Indexed: 01/25/2023]
Abstract
There has been conflicting evidence from meta-analyses on the effect of polyunsaturated fatty acids (PUFA) on non-alcoholic fatty liver disease (NAFLD). Therefore, in this umbrella meta-analysis, we are evaluating whether omega-3 PUFA supplementation has any benefit in treating NAFLD. Electronic databases such as PubMed, Web of Science, Scopus, Embase and Google Scholar were assessed to October 2022. This meta-analysis included all meta-analyses that examined the effect of PUFAs on liver fat and liver function tests [aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT)]. Meta-analysis was conducted using a random effects model. Subgroup analyses and sensitivity analyses were also performed. In total, eight articles involving 6,561 participants met the eligibility criteria. Advantageous impacts PUFA supplementation were observed on ALT (ESWMD = -6.72 IU/L; 95% CI: -8.61, -4.84; p < 0.001, and ESSMD = -0.52 IU/L; 95% CI: -0.84, -0.20, p < 0.001), AST (ESWMD = -3.73 IU/L, 95% CI: -5.93, -1.53, p < 0.001, and ESSMD = -0.65 IU/L; 95% CI: -1.08, -0.22, p = 0.003), GGT levels (ESWMD = -4.20 IU/L, 95% CI: -6.85, -1.55, p = 0.002), and liver fat (ESWMD = -5.16; 95% CI: -8.49, -1.82, p < 0.001). Intervention with omega-3 PUFAs improves ALT, AST, GGT, and liver fat in patients with NAFLD. Thus, omega-3 PUFAs could be considered as a therapeutic option in the treatment of NAFLD.
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Affiliation(s)
- Vali Musazadeh
- Student Research Committee, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Arash Karimi
- Nutrition Research Center, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran.,Nutrition Research Center, Department of Clinical Nutrition, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mahsa Malekahmadi
- Nutrition Department, Faculty of Medicine, Mashhad University of Medical Science, Mashhad, Iran
| | - Sana Sedgh Ahrabi
- Student Research Committee, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Parvin Dehghan
- Nutrition Research Center, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
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Kavyani Z, Dehghan P, Khani M, Khalafi M, Rosenkranz SK. The effects of camelina sativa oil and high-intensity interval training on liver function and metabolic outcomes in male type 2 diabetic rats. Front Nutr 2023; 10:1102862. [PMID: 36937342 PMCID: PMC10014722 DOI: 10.3389/fnut.2023.1102862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Accepted: 01/27/2023] [Indexed: 03/05/2023] Open
Abstract
Objectives The purpose of this study was to evaluate the independent and combined effects of camelina sativa oil and high-intensity interval training (HIIT) on liver function, and metabolic outcomes in streptozotocin-induced diabetic rats. Methods Forty male Wistar rats were randomly assigned to five equal groups (8 per group): Normal control (NC), diabetic control (DC), diabetic + camelina sativa oil (300 mg/kg by oral gavage per day; D + CSO), diabetic + HIIT (running on a treadmill 5 days/week for 8 weeks; D + HIIT), diabetic + camelina sativa oil + HIIT (D + CSO + HIIT). Results In all three intervention groups (D + CSO, D + HIIT, and D + CSO + HIIT) compared to the DC, hepatic TNF-α, MDA, and histopathology markers, decreased and hepatic PGC-1α, and PPAR-γ increased (p < 0.05). However, the effect of D + CSO was greater than D + HIIT alone. Hepatic TG decreased significantly in D + HIIT and D + CSO + HIIT compared to other groups (p < 0.001). Fasting plasma glucose in all three intervention groups (D + CSO, D + HIIT, and D + CSO + HIIT) and HOMA-IR in D + CSO and D + CSO + HIIT were decreased compared to DC (p < 0.001). Only hepatic TAC and fasting plasma insulin remained unaffected in the three diabetic groups (p < 0.001). Overall, D + CSO + HIIT had the largest effect on all outcomes. Conclusions At the doses and treatment duration used in the current study, combination of CSO and HIIT was beneficial for reducing liver function and metabolic outcomes other than CSO and HIIT alone.
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Affiliation(s)
- Zeynab Kavyani
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Biochemistry and Nutrition Therapy, School of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Parvin Dehghan
- Nutrition Research Center, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
- *Correspondence: Parvin Dehghan,
| | - Mostafa Khani
- Faculty of Physical Education and Sport Sciences, University of Tabriz, Tabriz, Iran
| | - Mousa Khalafi
- Department of Physical Education and Sport Sciences, Faculty of Humanities, University of Kashan, Kashan, Iran
| | - Sara K. Rosenkranz
- Department of Kinesiology and Nutrition Sciences, University of Nevada Las Vegas, Las Vegas, NV, United States
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Venegas-Calerón M, Napier JA. New alternative sources of omega-3 fish oil. ADVANCES IN FOOD AND NUTRITION RESEARCH 2023. [PMID: 37516467 DOI: 10.1016/bs.afnr.2023.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/08/2023]
Abstract
Long-chain omega-3 polyunsaturated fatty acids such as eicosapentaenoic and docosahexaenoic acids play an important role in brain growth and development, as well as in the health of the body. These fatty acids are traditionally found in seafood, such as fish, fish oils, and algae. They can also be added to food or consumed through dietary supplements. Due to a lack of supply to meet current demand and the potential for adverse effects from excessive consumption of fish and seafood, new alternatives are being sought to achieve the recommended levels in a safe and sustainable manner. New sources have been studied and new production mechanisms have been developed. These new proposals, as well as the importance of these fatty acids, are discussed in this paper.
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Alagawany M, Elnesr SS, Farag MR, El-Sabrout K, Alqaisi O, Dawood MAO, Soomro H, Abdelnour SA. Nutritional significance and health benefits of omega-3, -6 and -9 fatty acids in animals. Anim Biotechnol 2022; 33:1678-1690. [PMID: 33470155 DOI: 10.1080/10495398.2020.1869562] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
The balance between omega-3 (ω-3), omega-6 (ω-6) and omega-9 (ω-9) fatty acids (FAs) is very important because these types of oils constitute essential components for the formation of the cell membrane, also they are precursors for a large number of substances in the body. One of the most important strategies for improving the increment of polyunsaturated FAs in poultry and animal meat is the dietary administration of these FAs. Additionally, the different sources of ω-3 or 6 in the diet improve the performance, public health and physiological aspects including anti-oxidative properties and immunity. ω-3 FAs have anti-inflammatory characteristics due to their ability to reduce cytokines liberation. High-level of ω-6 FAs is always associated with an increased incidence of dangerous disorders like depression and heart disease. These FAs showed a tremendous series of beneficial impacts like improved cholesterol levels and a decreased occurrence of coronary heart diseases. This article includes some information on the use of ω-3, ω-6 and ω-9 FAs in animal and human diets. These oils are vital for the physiological and health aspects, and the information mentioned here will improve our understanding of the functions and roles of these FAs in the body.
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Affiliation(s)
- Mahmoud Alagawany
- Faculty of Agriculture, Department of Poultry, Zagazig University, Zagazig, Egypt
| | - Shaaban S Elnesr
- Faculty of Agriculture, Department of Poultry Production, Fayoum University, Fayoum, Egypt
| | - Mayada R Farag
- Faculty of Veterinary Medicine, Forensic Medicine and Toxicology Department, Zagazig University, Zagazig, Egypt
| | - Karim El-Sabrout
- Faculty of Agriculture (El-Shatby), Department of Poultry Production, Alexandria University, Alexandria, Egypt
| | - Othman Alqaisi
- College of Agricultural & Marine Sciences, Animal and Veterinary Sciences Department, Sultan Qaboos University, Muscat, Sultanate of Oman
| | - Mahmoud A O Dawood
- Faculty of Agriculture, Department of Animal Production, Kafrelsheikh University, Kafrelsheikh, Egypt
| | - Hidayatullah Soomro
- Faculty of Animal Production and Technology, Department of Poultry Production, Shaheed Benazir Bhutto University of Veterinary and Animal Science Sakrand, Sakrand, Pakistan
| | - Sameh A Abdelnour
- Faculty of Agriculture, Animal Production Department, Zagazig University, Zagazig, Egypt
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Ramadan NM, Elmasry K, Elsayed HRH, El-Mesery A, Eraky SM. The hepatoprotective effects of n3-polyunsaturated fatty acids against non-alcoholic fatty liver disease in diabetic rats through the FOXO1/PPARα/GABARAPL1 signalling pathway. Life Sci 2022; 311:121145. [DOI: 10.1016/j.lfs.2022.121145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Revised: 10/26/2022] [Accepted: 10/29/2022] [Indexed: 11/06/2022]
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Chen G, Zhang Y, Zhang K, Tian G, Bai S, Ding X, Wang J, Lv L, Tan Q, Zhao W, Zeng Q. Effects of Dietary Zinc Deficiency on Skin Breaking Strength and Fatty Acid Composition in Broiler Chickens and Pekin Ducks. Biol Trace Elem Res 2022:10.1007/s12011-022-03490-2. [PMID: 36396781 DOI: 10.1007/s12011-022-03490-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 11/13/2022] [Indexed: 11/18/2022]
Abstract
This study is aimed at investigating the effect of dietary zinc deficiency (ZnD) on skin breaking strength and skin chemical and fatty acid composition in broiler chickens and Pekin ducks. A total of 200 1-day-old male broiler chickens and 200 1-day-old male ducklings were used in a 2 × 2 factorial design and randomly allocated to 4 treatments with 10 replicated cages of 10 birds per cage. Diets containing zinc at 84.77 mg/kg and 20.42 mg/kg were regarded as the control diet and zinc-deficient diet, respectively. The results showed the following: (1) dietary ZnD decreased (P < 0.05) the breast skin weight (day 21), breast skin index (day 21), skin fat content (day 7), and skin Zn content (days 7, 14, and 21) of ducks, but only increased (P < 0.05) the skin fat content of broiler chickens at 7 days of age; ducks had a higher (P < 0.05) breast skin weight, breast skin index, and skin breaking strength as well as a lower skin fat content (days 7 and 14) than those in broiler chickens. (2) Dietary ZnD decreased the content of myristic acid (day 21) and increased the content of oleic acid (day 7) content in the skin of ducks and increased the palmitic acid (day 7) content in the skin of broiler chickens (P < 0.05) and increased the MUFA (day 7) content in the skin and the atherogenic index (day 21) in ducks. The contents of myristic acid (day 21), stearic acid (day 21), and oleic acid (days 7, 14, and 21) in the skin of broiler chickens were lower (P < 0.05) than those in ducks of the same age. In conclusion, using skin weight, skin index and skin MUFA content as criteria, the results indicated that meat ducks were more sensitive to dietary ZnD than broiler chickens. Using skin fat content as criterion, the results indicated that broiler chickens were more sensitive to dietary ZnD than meat ducks.
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Affiliation(s)
- Guanhua Chen
- Animal Nutrition Institute, Sichuan Agricultural University, No. 211 Huimin Road, Wenjiang, Chengdu, 611130, Sichuan, China
| | - Yang Zhang
- Habio Bio-Tech Co. Ltd, Mianyang, 61000, China
| | - Keying Zhang
- Animal Nutrition Institute, Sichuan Agricultural University, No. 211 Huimin Road, Wenjiang, Chengdu, 611130, Sichuan, China
| | - Gang Tian
- Animal Nutrition Institute, Sichuan Agricultural University, No. 211 Huimin Road, Wenjiang, Chengdu, 611130, Sichuan, China
| | - Shiping Bai
- Animal Nutrition Institute, Sichuan Agricultural University, No. 211 Huimin Road, Wenjiang, Chengdu, 611130, Sichuan, China
| | - Xuemei Ding
- Animal Nutrition Institute, Sichuan Agricultural University, No. 211 Huimin Road, Wenjiang, Chengdu, 611130, Sichuan, China
| | - Jianping Wang
- Animal Nutrition Institute, Sichuan Agricultural University, No. 211 Huimin Road, Wenjiang, Chengdu, 611130, Sichuan, China
| | - Li Lv
- Animal Nutrition Institute, Sichuan Agricultural University, No. 211 Huimin Road, Wenjiang, Chengdu, 611130, Sichuan, China
| | - Quan Tan
- Novus International Trading (Shanghai), Co., Ltd, Shanghai, 200080, China
| | - Wei Zhao
- Novus International Trading (Shanghai), Co., Ltd, Shanghai, 200080, China
| | - Qiufeng Zeng
- Animal Nutrition Institute, Sichuan Agricultural University, No. 211 Huimin Road, Wenjiang, Chengdu, 611130, Sichuan, China.
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Bae SJ, Bak SB, Kim YW. Coordination of AMPK and YAP by Spatholobi Caulis and Procyanidin B2 Provides Antioxidant Effects In Vitro and In Vivo. Int J Mol Sci 2022; 23:ijms232213730. [PMID: 36430207 PMCID: PMC9694094 DOI: 10.3390/ijms232213730] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 11/01/2022] [Accepted: 11/06/2022] [Indexed: 11/09/2022] Open
Abstract
The liver is vulnerable to oxidative attacks from heavy metals, such as iron, as well as some drugs, including acetaminophen. It has been shown that enhanced oxidative stress in the liver leads to excessive ROS production and mitochondrial dysfunction, resulting in organ injury. The beneficial effects of Spatholobi Caulis (SC), a natural herbal medicine, include treating ischemic stroke, inhibiting tumor cell invasion, pro-angiogenic activities, and anti-inflammatory properties. Scientific studies on its effects against hepatotoxic reagents (e.g., iron and acetaminophen), as well as their underlying mechanisms, are insufficient. This study examined the antioxidant effects and mechanisms of SC in vitro and in vivo. In cells, the proinflammatory mediator, arachidonic acid (AA), plus iron, significantly induced an increase in ROS generation, the damage in mitochondrial membrane potential, and the resulting apoptosis, which were markedly blocked by SC. More importantly, SC affected the activation of AMP-activated protein kinase (AMPK)-related proteins, which were vital to regulating oxidative stress in cells. In addition, SC mediated the expression of Yes-associated protein (YAP)-related proteins. Among the active compounds in SC, the procyanidin B2, but not liquiritigenin, daidzein, and genistein, significantly inhibited the cytotoxicity induced by AA + iron, and activated the LKB1-AMPK pathway. In mice, the oral administration of SC alleviated the elevations of ALT and histological changes by the acetaminophen-induced liver injury. These results reveal the potential of SC and a key bioactive component, procyanidin B2, as antioxidant candidates for hepatoprotection.
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El-Agawy MSED, Badawy AMM, Rabei MR, Elshaer MMA, El Nashar EM, Alghamdi MA, Alshehri MA, Elsayed HRH. Methotrexate-Induced Alteration of Renal Aquaporins 1 and 2, Oxidative Stress and Tubular Apoptosis Can Be Attenuated by Omega-3 Fatty Acids Supplementation. Int J Mol Sci 2022; 23:12794. [PMID: 36361584 PMCID: PMC9653681 DOI: 10.3390/ijms232112794] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Revised: 10/08/2022] [Accepted: 10/19/2022] [Indexed: 09/10/2023] Open
Abstract
Methotrexate (MTX) is a potent anti-cancer drug, commonly associated with nephrotoxicity via the induction of oxidative stress and apoptosis with alteration of renal water channel proteins, namely aquaporins (AQPs). Omega-3 long-chain polyunsaturated fatty acids (LC-PUFA) have shown cytoprotective effects through their anti-oxidant and antiapoptotic activities. The present study aims for the first time to explore the role of LC-PUFA against MTX-induced nephrotoxicity. Rats were divided into the following groups: saline control, LC-PUFA control, MTX, MTX + LC-PUFA (150 mg/kg), or MTX + LC-PUFA (300 mg/kg). Then, H&E staining and immunohistochemical staining for the anti-apoptosis marker B-cell lymphoma 2 (BCL-2), the apoptosis marker BCL2-Associated X Protein (BAX), the proinflammatory marker Nuclear factor kappa B (NF-kB), AQPs 1 and 2 were performed in kidney sections with an assessment of renal oxidative stress. The MTX caused a renal histopathological alteration, upregulated renal BAX and NF-kB, downregulated Bcl-2 and AQP1, altered the distribution of AQP2, and caused oxidative stress. The LC-PUFA attenuated the pathological changes and decreased renal BAX and NF-kB, increased BCL-2 and AQP1, restored the normal distribution of AQP2, and decreased the oxidative stress. Therefore, LC-PUFA is a good adjuvant to MTX to prevent its adverse effects on kidneys through its antiapoptotic, antioxidant, and anti-inflammatory effect and its role in the restoration of the expression of AQPs 1 and 2.
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Affiliation(s)
- Mosaab Salah El-din El-Agawy
- Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
- Department of Anatomy, Faculty of Medicine, New Mansoura University, New Mansoura 35712, Egypt
| | | | - Mohammed R. Rabei
- Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
- Department of Physiology, Faculty of Medicine, King Salman International University, South Sinai 46511, Egypt
| | - Mohamed Mahmoud Abdelraheem Elshaer
- Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt
- Department of Clinical Pharmacology, Faculty of Medicine, King Salman International University, South Sinai 46511, Egypt
| | - Eman Mohamad El Nashar
- Department of Anatomy, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia
- Department of Histology and Cell Biology, Faculty of Medicine, Benha University, Benha 13511, Egypt
| | - Mansour A. Alghamdi
- Department of Anatomy, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia
- Genomics and Personalized Medicine Unit, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia
| | - Mohammed A. Alshehri
- Nephrology Section, Internal Medicine Department, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia
| | - Hassan Reda Hassan Elsayed
- Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
- Department of Anatomy, Faculty of Medicine, New Mansoura University, New Mansoura 35712, Egypt
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Maksymchuk O, Shysh A, Stroy D. Treatment with omega-3 PUFAs does not increase the risk of CYP2E1-dependent oxidative stress and diabetic liver pathology. Front Endocrinol (Lausanne) 2022; 13:1004564. [PMID: 36225205 PMCID: PMC9550212 DOI: 10.3389/fendo.2022.1004564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 08/30/2022] [Indexed: 11/13/2022] Open
Abstract
An increase in CYP2E1 expression is a key factor in the development of diabetic oxidative liver damage. Long-term treatment with omega-3 PUFAs, which are CYP2E1 substrates, may affect CYP2E1 expression in the liver. In this work, we performed Western blot analysis, biochemical methods, and microscopic ultrastructural studies of the liver in a streptozotocin-induced rat model of type 1 diabetes to investigate whether long-term treatment with omega-3 PUFAs could induce CYP2E1-dependent oxidative stress and diabetic liver pathology. Significant hyperglycemia and lack of natural weight gain were observed in the diabetic rats compared to non-diabetic controls. A 2.5-fold increase in CYP2E1 expression (protein content and activity) was also observed in the diabetic rats. In addition, signs of oxidative stress were found in the liver of the diabetic rats. A significant increase in transaminases and GGT level in blood serum was also observed, which could indicate marked destruction of liver tissue. Diabetic dyslipidemia (increased triacylglycerol levels and decreased HDL-C levels) was found. Treatment of the diabetic animals with an omega-3-enriched pharmaceutical composition of PUFAs had no effect on CYP2E1 levels but contributed to a two-fold decrease in enzyme activity. The intensity of lipid peroxidation also remained close to the diabetic group. However, at the same time, antioxidant protection was provided by induction of antioxidant enzyme activity. Examination of the liver ultrastructure revealed no characteristic signs of diabetic pathology. However, omega-3 PUFAs did not normalize blood glucose levels and serum lipid profile. Thus, long-term treatment of diabetic rats with omega-3 PUFAs does not increase the risk of CYP2E1-dependent oxidative stress and development of liver pathology but prevents some diabetic ultrastructural damage to hepatocytes.
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Affiliation(s)
- Oksana Maksymchuk
- Department of Molecular Oncogenetics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv, Ukraine
| | - Angela Shysh
- Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
| | - Dmytro Stroy
- Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
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Xie P, Guo M, Xie JB, Xiao MY, Qi YS, Duan Y, Li FF, Piao XL. Effects of heat-processed Gynostemma pentaphyllum on high-fat diet-fed mice of obesity and functional analysis on network pharmacology and molecular docking strategy. JOURNAL OF ETHNOPHARMACOLOGY 2022; 294:115335. [PMID: 35513215 DOI: 10.1016/j.jep.2022.115335] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 04/12/2022] [Accepted: 04/28/2022] [Indexed: 06/14/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Gynostemma pentaphyllum has been used as traditional medicine for many diseases, including metabolic syndrome (Mets), aging, diabetes, neurodegenerative diseases in China, some East Asian and Southeast Asian countries. It was shown that G. pentaphyllum and gypenosides had anti-obesity and cholesterol-lowering effects too. However, its main active ingredients are still unclear. AIMS The objective of this study was to compare the effects of gypenosides before and after heat-processing on high fat obese mice, and to analyze the function of G. pentaphyllum saponin via network pharmacology and molecular docking. METHODS The leaves of G. pentaphyllum were heat processed at 120 °C for 3 h to obtain heat-processed G. pentaphyllum. Gypenosides (Gyp) and heat-processed gypenosides (HGyp) were prepared by resin HP-20 chromatography and analyzed using LC-MS from the extracts of G. pentaphyllum before and after heat-processing, respectively. Obesity model was made with high fat diet (HFD). Gyp and HGyp were administrated at 100 mg/kg for 12 weeks in HFD obese mice and the body weight, energy intake, and levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL) were compared. HGyp was administrated at a dose of 50,100,200 mg/kg for 12 weeks in HFD obese mice and the perirenal adipose, epididymal adipose, abdominal adipose, shoulder brown adipose, inguinal adipose were measured. Moreover, the potential targets, hub genes and pathways of damulin A, damulin B, gypenoside L, gypenoside LI for treating Mets were screened out via network pharmacology. According to the results of network pharmacology, core targets of treating Mets were docking with damulin A, gypenoside L, damulin B, gypenoside LI via molecular docking. RESULTS HGyp showed stronger effects on body weight loss and lipid-lowering in obese mice than Gyp. The contents of gypenoside L, gypenoside LI, damulin A and damulin B of G. pentaphyllum were increased by heat-processing. HGyp significantly decreased the body weight, calorie intake, and levels of TC, TG, LDL, HDL on the obese mice. It up-regulated PPARα and PPARγ in the liver tissues. HGyp reduced significantly the size of adipocytes in inguinal, abdominal, epididymal adipose and increased the proportion of interscapular brown fat. Network pharmacology results showed that 21 potential targets and 12 related-pathways were screened out. HMGCR, ACE, LIPC, LIPG, PPARα PPARδ, PPARγ were the core targets of HGyp against lipid metabolism by molecular docking. The putative functional targets of HGyp may be modulated by AGE-RAGE, TNF, glycerolipid metabolism, lipid and atherosclerosis, cholesterol metabolism, PPAR, fat digestion and absorption, cell adhesion molecules signaling pathway. CONCLUSIONS Gyp and HGyp are valuable for inhibition obesity, lipid-lowering, metabolic regulation. Especially, the effect of HGyp is better than that of Gyp.
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Affiliation(s)
- Peng Xie
- School of Pharmacy, Minzu University of China, Beijing, 100081, China
| | - Mei Guo
- School of Pharmacy, Minzu University of China, Beijing, 100081, China
| | - Jin-Bo Xie
- School of Pharmacy, Minzu University of China, Beijing, 100081, China
| | - Man-Yu Xiao
- School of Pharmacy, Minzu University of China, Beijing, 100081, China
| | - Yan-Shuang Qi
- School of Pharmacy, Minzu University of China, Beijing, 100081, China
| | - Yu Duan
- School of Pharmacy, Minzu University of China, Beijing, 100081, China
| | - Fang-Fang Li
- School of Pharmacy, Minzu University of China, Beijing, 100081, China
| | - Xiang-Lan Piao
- School of Pharmacy, Minzu University of China, Beijing, 100081, China.
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Machado M, Costa EM, Silva S, Rodriguez-Alcalá LM, Gomes AM, Pintado M. Pomegranate Oil’s Potential as an Anti-Obesity Ingredient. Molecules 2022; 27:molecules27154958. [PMID: 35956908 PMCID: PMC9370579 DOI: 10.3390/molecules27154958] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 07/28/2022] [Accepted: 07/31/2022] [Indexed: 11/16/2022] Open
Abstract
In recent years, pomegranate oil has obtained more attention due to its content of conjugated linolenic acids and possible application in the prevention of many diseases. The purpose of this work was to evaluate the potential ability of pomegranate oil to modulate obesity-related metabolism and immune response using in vitro models. In this regard, pomegranate oil was characterized in terms of fatty acids profile, tocopherols and phytosterols, and antioxidant capacity. After evaluation of the safety profile, pomegranate oil’s capacity to modulate obesity-related metabolism was evaluated through adipolysis and adipokines secretion quantification in 3T3-L1 differentiated adipocytes and hepatic lipid accumulation assay in Hep G2 hepatocytes. The immunomodulatory activity was evaluated in Caco-2 cells by quantification of pro-inflammatory cytokines IL-6, IL-8, and TNF-α. This oil showed high antioxidant capacity and was mainly composed of conjugated fatty acid, namely punicic acid. Its chemical composition was responsible for its capacity to reduce the lipid accumulation in Hep G2 cells and 3T3-L1 differentiated adipocytes. In short, pomegranate oil shows great potential for the development of functional foods and nutraceuticals targeting obesity.
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Tan LJ, Shin S. Effects of oily fish and its fatty acid intake on non-alcoholic fatty liver disease development among South Korean adults. Front Nutr 2022; 9:876909. [PMID: 35938102 PMCID: PMC9353947 DOI: 10.3389/fnut.2022.876909] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 06/28/2022] [Indexed: 12/02/2022] Open
Abstract
Background The benefits of fish fatty acid intake for non-alcoholic fatty liver disease (NAFLD) are rarely reported, although a previous study assessed the relationship between oily fish consumption and the prevalence of NAFLD. Aims We investigated whether oily fish and fish-based monounsaturated fatty acids, polyunsaturated fatty acids, and omega-3 fatty acids affect the development of NAFLD in South Korean adults. Methods In this large-scale cohort study, 44,139 participants of the Health Examinees study were selected for analysis after 5 years of follow-up. NAFLD is diagnosed with a non-invasive index, the fatty liver index. Using multivariable Cox proportional hazards models, adjusted for age, body mass index, total energy intake, education, physical activity, smoking status, and drinking (alcohol) status, we calculated the hazard ratios and 95% confidence intervals. Results For men, NAFLD had no statistically significant associations with quartiles of total oily fish or its fatty acid intake. However, among women, an inverse association was observed (all p for trend <0.05). Regarding the standard deviation (SD) increment of total oily fish or its fatty acid intake by one, all fatty acids from oily fish showed inverse associations for NAFLD in both men and women. After stratified analyses, we found that drinking status and menopause status were independent risk factors for NAFLD. Oily fish or its fatty acid intake has the same benefit pattern on metabolic dysfunction-associated fatty liver disease as NAFLD. Conclusion Oily fish and its fatty acid intake showed a preventative benefit for NAFLD and metabolic dysfunction-associated fatty liver disease, especially in South Korean women.
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Occhiuto C, Aliberto G, Ingegneri M, Trombetta D, Circosta C, Smeriglio A. Comparative Evaluation of the Nutrients, Phytochemicals, and Antioxidant Activity of Two Hempseed Oils and Their Byproducts after Cold Pressing. Molecules 2022; 27:3431. [PMID: 35684369 PMCID: PMC9181874 DOI: 10.3390/molecules27113431] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 05/18/2022] [Accepted: 05/24/2022] [Indexed: 11/17/2022] Open
Abstract
Recently, there has been a growing interest in the recovery of agri-food waste within the circular economy perspective. In this study, the nutritional, phytochemical, and biological features of the cold-pressed hempseed oil (HSO) and hempseed meal (HSM) of two industrial hemp varieties (USO 31 and Futura 75, THC ≤ 0.2%) were evaluated. The HSOs showed a high total phenols and flavonoid content, which were confirmed by LC-DAD-ESI-MS analysis, with rutin as the most abundant compound (56.93-77.89 µg/100 FW). They also proved to be a rich source of tocopherols (81.69-101.45 mg/100 g FW) and of a well-balanced ω-6 to ω-3 fatty acid ratio (3:1) with USO 31, which showed the best phytochemical profile and consequently the best antioxidant activity (about two times higher than Futura 75). The HSMs still retained part of the phytochemicals identified in the HSOs (polyphenols, tocopherols, and the preserved ω-6/ω-3 fatty acids ratio) and a modest antioxidant activity. Furthermore, they showed a very interesting nutritional profile, which was very rich in proteins (29.88-31.44 g/100 g FW), crude fibers (18.39-19.67 g/100 g), and essential and non-essential amino acids. Finally, only a restrained amount of anti-nutritional factors (trypsin inhibitors, phytic acid, and condensed tannins) was found, suggesting a promising re-use of these byproducts in the nutraceutical field.
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Affiliation(s)
- Cristina Occhiuto
- Foundation “Prof. Antonio Imbesi”, University of Messina, Piazza Pugliatti 1, 98122 Messina, Italy; (C.O.); (G.A.)
| | - Gianluigi Aliberto
- Foundation “Prof. Antonio Imbesi”, University of Messina, Piazza Pugliatti 1, 98122 Messina, Italy; (C.O.); (G.A.)
| | - Mariarosaria Ingegneri
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres 31, 98166 Messina, Italy; (M.I.); (C.C.); (A.S.)
| | - Domenico Trombetta
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres 31, 98166 Messina, Italy; (M.I.); (C.C.); (A.S.)
| | - Clara Circosta
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres 31, 98166 Messina, Italy; (M.I.); (C.C.); (A.S.)
| | - Antonella Smeriglio
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres 31, 98166 Messina, Italy; (M.I.); (C.C.); (A.S.)
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Efficacy of omega-3-rich Camelina sativa on the metabolic and clinical markers in nonalcoholic fatty liver disease: a randomized, controlled trial. Eur J Gastroenterol Hepatol 2022; 34:537-545. [PMID: 35421019 DOI: 10.1097/meg.0000000000002297] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Recently, omega-3 fatty acids and antioxidants co-supplementation was considered as alternative treatment in the management of nonalcoholic fatty liver disease (NAFLD). This trial evaluated effects of Camelina sativa oil (CSO) as a rich source of omega-3 fatty acids and antioxidants on anthropometric indices, lipid profile, liver enzymes, and adiponectin in NAFLD patients. PARTICIPANTS AND METHODS This triple-blind, placebo-controlled, randomized clinical trial was conducted on 46 NAFLD patients who were randomly assigned to either a CSO supplement or placebo for 12 weeks. Both groups received a loss weight diet. Levels of liver enzymes, adiponectin, lipid profile, atherogenic index, and anthropometric indices were assessed for all patients at baseline and post-intervention. RESULTS CSO caused significant differences in weight, BMI, waist circumference, waist-to-hip ratio, triglyceride, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), TC/HDL-c, LDL-c/HDL-c, atherogenic index, alanine aminotransferase, and adiponectin concentrations in the CSO group compared with the placebo group (P < 0.046 for all). No significant differences were found in hip circumference, neck circumference, HDL-c, and other liver enzymes in the CSO group compared with the placebo group (P = 0.790, P = 0.091, P = 0.149, P < 0.159 for liver enzymes, respectively). DISCUSSION AND CONCLUSION This study showed that CSO supplementation for 12 weeks causes significant changes in all of anthropometric indices (except hip circumference and neck circumference), ALT, lipid profile (except HDL-c), atherogenic index, and adiponectin in NAFLD patients.
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Madsen PA, Curtasu MV, Canibe N, Hedemann MS, Pedersen MLM, Lauridsen C. Non-targeted metabolomics of saliva to explore potential biomarkers for gastric ulceration in pigs fed hemp. Animal 2022; 16:100477. [PMID: 35247704 DOI: 10.1016/j.animal.2022.100477] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 01/26/2022] [Accepted: 01/27/2022] [Indexed: 11/17/2022] Open
Abstract
Gastric ulceration is a common disease in pig production worldwide and is associated with economic losses as well as animal health and welfare issues. The aim of this study was to explore potential salivary biomarkers for gastric ulceration in pigs. In addition, the aim was to study the effect of hemp on the incidence of gastric ulcers. Approximately 440 growing-finishing pigs in the period from 30 to 110 kg BW were allocated to four different diets: meal feed (Meal); pelleted feed (Pellets); pelleted feed added 4% hempseed cake (Hemp Cake); pelleted feed added 4% hempseed hulls (Hemp Hulls). The day before slaughter, saliva samples from each pig were collected. After slaughter, the stomachs were emptied to assess the consistency of the stomach content and examined for gastric ulceration using an index scale (0-10). Noticeable changes of the gastric mucosa (total index score ≥ 6) were observed in 291 pigs. The odds of having index scores 0-5 relative to index scores 6-8 and 9-10, respectively, were higher (P < 0.001) for pigs fed Meal compared to pigs fed Pellets. The odds of suffering from severe gastric ulcers tended (P = 0.08) to be lower in pigs fed Hemp Hulls compared to pigs fed Pellets. A non-targeted liquid chromatography mass spectrometry based metabolomics analysis was performed on saliva samples to determine any separation between pigs with healthy stomachs and those with gastric ulcers and to examine a possible correlation between gastric ulcer index and potential biomarkers. Partial least-squares discriminant analysis showed a separation between pigs with ulcers and those with healthy stomachs/hyperkeratosis (HK). Metabolites contributing to the separation between groups were identified. Levels of oxylipins deriving from linoleic acid were lower (P < 0.001) in pigs with ulcers compared to healthy/HK pigs. This may indicate a shift in the metabolic pathways towards more pro-inflammatory arachidonic acid-derived eicosanoids, which might reflect an increased inflammatory response. Thus, reduced levels of oxylipins derived from linoleic acid seemed to be associated with active gastric ulcers, and thereby they might function as biomarkers for gastric ulceration in pigs. In addition, supplementation of hempseed hulls had a beneficial effect on severe gastric ulcers, as hempseed hulls changed the consistency of the gastric content by conferring more solidness. However, it was not possible to observe any reliable separation between pigs fed pellets supplemented with hemp products and pigs fed non-supplemented pellets according to the identified salivary metabolites.
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Affiliation(s)
- P A Madsen
- Department of Animal Science, Aarhus University, AU Foulum, Blichers Allé 20, 8830 Tjele, Denmark
| | - M V Curtasu
- Laval University, Faculty of Agriculture and Food Sciences, Department of Animal Sciences, 2425 rue de l'Agriculture, Québec G1V 0A6, Canada
| | - N Canibe
- Department of Animal Science, Aarhus University, AU Foulum, Blichers Allé 20, 8830 Tjele, Denmark
| | - M S Hedemann
- Department of Animal Science, Aarhus University, AU Foulum, Blichers Allé 20, 8830 Tjele, Denmark
| | - M L M Pedersen
- SEGES Pig Research Centre, Axeltorv 3, 1609 Copenhagen, Denmark
| | - C Lauridsen
- Department of Animal Science, Aarhus University, AU Foulum, Blichers Allé 20, 8830 Tjele, Denmark.
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Carlson Z, Hafner H, El Habbal N, Harman E, Liu S, Botezatu N, Alharastani M, Rivet C, Reynolds H, Both N, Sun H, Bridges D, Gregg B. Short Term Changes in Dietary Fat Content and Metformin Treatment During Lactation Impact Milk Composition and Mammary Gland Morphology. J Mammary Gland Biol Neoplasia 2022; 27:1-18. [PMID: 35137304 DOI: 10.1007/s10911-022-09512-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Accepted: 01/24/2022] [Indexed: 11/30/2022] Open
Abstract
Maternal health and diet can have important consequences for offspring nutrition and metabolic health. During lactation, signals are communicated from the mother to the infant through milk via macronutrients, hormones, and bioactive molecules. In this study we designed experiments to probe the mother-milk-infant triad in the condition of normal maternal health and upon exposure to high fat diet (HFD) with or without concurrent metformin exposure. We examined maternal characteristics, milk composition and offspring metabolic parameters on postnatal day 16, prior to offspring weaning. We found that lactational HFD increased maternal adipose tissue weight, mammary gland adipocyte size, and altered milk lipid composition causing a higher amount of omega-6 (n6) long chain fatty acids and lower omega-3 (n3). Offspring of HFD dams were heavier with more body fat during suckling. Metformin (Met) exposure decreased maternal blood glucose and several milk amino acids. Offspring of met dams were smaller during suckling. Gene expression in the lactating mammary glands was impacted to a greater extent by metformin than HFD, but both metformin and HFD altered genes related to muscle contraction, indicating that these genes may be more susceptible to lactational stressors. Our study demonstrates the impact of common maternal exposures during lactation on milk composition, mammary gland function and offspring growth with metformin having little capacity to rescue the offspring from the effects of a maternal HFD during lactation.
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Affiliation(s)
- Zach Carlson
- Department of Pediatrics, Division of Diabetes, Endocrinology and Metabolism, University of Michigan Medicine, Ann Arbor, MI, USA
| | - Hannah Hafner
- Department of Pediatrics, Division of Diabetes, Endocrinology and Metabolism, University of Michigan Medicine, Ann Arbor, MI, USA
| | - Noura El Habbal
- Department of Nutritional Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA
| | - Emma Harman
- Department of Pediatrics, Division of Diabetes, Endocrinology and Metabolism, University of Michigan Medicine, Ann Arbor, MI, USA
- Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA
| | - Stephanie Liu
- Department of Pediatrics, Division of Diabetes, Endocrinology and Metabolism, University of Michigan Medicine, Ann Arbor, MI, USA
| | - Nathalie Botezatu
- Department of Pediatrics, Division of Diabetes, Endocrinology and Metabolism, University of Michigan Medicine, Ann Arbor, MI, USA
| | | | - Cecilia Rivet
- Department of Pediatrics, Division of Diabetes, Endocrinology and Metabolism, University of Michigan Medicine, Ann Arbor, MI, USA
| | - Holly Reynolds
- Department of Pediatrics, Division of Diabetes, Endocrinology and Metabolism, University of Michigan Medicine, Ann Arbor, MI, USA
| | - Nyahon Both
- Department of Nutritional Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA
| | - Haijing Sun
- Department of Pediatrics, Division of Diabetes, Endocrinology and Metabolism, University of Michigan Medicine, Ann Arbor, MI, USA
| | - Dave Bridges
- Department of Nutritional Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA
| | - Brigid Gregg
- Department of Pediatrics, Division of Diabetes, Endocrinology and Metabolism, University of Michigan Medicine, Ann Arbor, MI, USA.
- Department of Nutritional Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
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Chilton FH, Manichaikul A, Yang C, O'Connor TD, Johnstone LM, Blomquist S, Schembre SM, Sergeant S, Zec M, Tsai MY, Rich SS, Bridgewater SJ, Mathias RA, Hallmark B. Interpreting Clinical Trials With Omega-3 Supplements in the Context of Ancestry and FADS Genetic Variation. Front Nutr 2022; 8:808054. [PMID: 35211495 PMCID: PMC8861490 DOI: 10.3389/fnut.2021.808054] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 12/13/2021] [Indexed: 12/15/2022] Open
Abstract
Human diets in developed countries such as the US have changed dramatically over the past 75 years, leading to increased obesity, inflammation, and cardiometabolic dysfunction. Evidence over the past decade indicates that the interaction of genetic variation with changes in the intake of 18-carbon essential dietary omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA), linoleic acid (LA) and α-linolenic acid (ALA), respectively, has impacted numerous molecular and clinical phenotypes. Interactions are particularly relevant with the FADS1 and FADS2 genes, which encode key fatty acid desaturases in the pathway that converts LA and ALA to their long chain (≥20 carbons), highly unsaturated fatty acid (HUFA) counterparts. These gene by nutrient interactions affect the levels and balance of n-6 and n-3 HUFA that in turn are converted to a wide array of lipids with signaling roles, including eicosanoids, docosanoids, other oxylipins and endocannabinoids. With few exceptions, n-6 HUFA are precursors of pro-inflammatory/pro-thrombotic signaling lipids, and n-3 HUFA are generally anti-inflammatory/anti-thrombotic. We and others have demonstrated that African ancestry populations have much higher frequencies (vs. European-, Asian- or indigenous Americas-ancestry populations) of a FADS "derived" haplotype that is associated with the efficient conversion of high levels of dietary n-6 PUFA to pro-inflammatory n-6 HUFA. By contrast, an "ancestral" haplotype, carrying alleles associated with a limited capacity to synthesize HUFA, which can lead to n-3 HUFA deficiency, is found at high frequency in certain Hispanic populations and is nearly fixed in several indigenous populations from the Americas. Based on these observations, a focused secondary subgroup analysis of the VITAL n-3 HUFA supplementation trial stratifying the data based on self-reported ancestry revealed that African Americans may benefit from n-3 HUFA supplementation, and both ancestry and FADS variability should be factored into future clinical trials design.
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Affiliation(s)
- Floyd H. Chilton
- School of Nutritional Sciences and Wellness, University of Arizona, Tucson, AZ, United States
- BIO5 Institute, University of Arizona, Tucson, AZ, United States
| | - Ani Manichaikul
- Center for Public Health Genomics, University of Virginia, Charlottesville, VA, United States
| | - Chaojie Yang
- Center for Public Health Genomics, University of Virginia, Charlottesville, VA, United States
- Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, United States
| | - Timothy D. O'Connor
- Program in Personalized and Genomic Medicine, Department of Medicine, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Laurel M. Johnstone
- University of Arizona Genetics Core, University of Arizona, Tucson, AZ, United States
| | - Sarah Blomquist
- School of Nutritional Sciences and Wellness, University of Arizona, Tucson, AZ, United States
| | - Susan M. Schembre
- Department of Family and Community Medicine, College of Medicine-Tucson, University of Arizona, Tucson, AZ, United States
| | - Susan Sergeant
- Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, United States
| | - Manja Zec
- School of Nutritional Sciences and Wellness, University of Arizona, Tucson, AZ, United States
| | - Michael Y. Tsai
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, United States
| | - Stephen S. Rich
- Center for Public Health Genomics, University of Virginia, Charlottesville, VA, United States
| | | | - Rasika A. Mathias
- Department of Medicine, Johns Hopkins University, Baltimore, MD, United States
| | - Brian Hallmark
- Center for Biomedical Informatics and Biostatistics, BIO5 Institute, University of Arizona, Tucson, AZ, United States
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Effects of a low free sugar diet on the management of nonalcoholic fatty liver disease: a randomized clinical trial. Eur J Clin Nutr 2022; 76:987-994. [PMID: 35058605 DOI: 10.1038/s41430-022-01081-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 12/20/2021] [Accepted: 01/12/2022] [Indexed: 12/13/2022]
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50
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Onaolapo OJ, Odeniyi AO, Onaolapo AY. Parkinson's Disease: Is there a Role for Dietary and Herbal Supplements? CNS & NEUROLOGICAL DISORDERS DRUG TARGETS 2022; 20:343-365. [PMID: 33602107 DOI: 10.2174/1871527320666210218082954] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 09/19/2020] [Accepted: 09/29/2020] [Indexed: 12/18/2022]
Abstract
Parkinson's Disease (PD) is characterised by degeneration of the neurons of the nigrostriatal dopaminergic pathway of the brain. The pharmacological cornerstone of PD management is mainly the use of dopamine precursors, dopamine receptor agonists, and agents that inhibit the biochemical degradation of dopamine. While these drugs initially provide relief to the symptoms and improve the quality of life of the patients, progression of the underlying pathological processes, such as oxidative stress and neuroinflammation (which have been strongly associated with PD and other neurodegenerative disorders), eventually reduce their benefits, making further benefits achievable, only at high doses due to which the magnitude and frequency of side-effects are amplified. Also, while it is becoming obvious that mainstream pharmacological agents may not always provide the much-needed answer, the question remains what succour can nature provide through dietary supplements, nutraceuticals and herbal remedies? This narrative review examines current literature for evidence of the possible roles (if any) of nutraceuticals, dietary supplements and herbal remedies in the prevention or management of PD by examining how these compounds could modulate key factors and pathways that are crucial to the pathogenesis and/or progression of PD. The likely limitations of this approach and its possible future roles in PD prevention and management are also considered.
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Affiliation(s)
- Olakunle J Onaolapo
- Behavioural Neuroscience Unit, Neuropharmacology Subdivision, Department of Pharmacology, Ladoke Akintola University of Technology, Osogbo, Osun State, Nigeria
| | - Ademola O Odeniyi
- Behavioural Neuroscience Unit, Neuropharmacology Subdivision, Department of Pharmacology, Ladoke Akintola University of Technology, Osogbo, Osun State, Nigeria
| | - Adejoke Y Onaolapo
- Behavioural Neuroscience Unit, Neurobiology Subdivision, Department of Anatomy, Ladoke Akintola University of Technology, Ogbomosho, Oyo State, Nigeria
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