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Rajewski P, Cieściński J, Rajewski P, Suwała S, Rajewska A, Potasz M. Dietary Interventions and Physical Activity as Crucial Factors in the Prevention and Treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease. Biomedicines 2025; 13:217. [PMID: 39857800 PMCID: PMC11760440 DOI: 10.3390/biomedicines13010217] [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: 12/21/2024] [Revised: 01/09/2025] [Accepted: 01/14/2025] [Indexed: 01/27/2025] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and affects nearly 30% of the adult population and 10% of the pediatric population. It is estimated that this number will double by 2030. MASLD is one of the leading causes of hepatocellular carcinoma, cirrhosis, and liver transplantation, as well as a significant risk factor for cardiovascular disease and mortality. Due to the ever-increasing number of patients, the long-term asymptomatic course of the disease, serious complications, and lack of preventive programs, as well as insufficient awareness of the disease among patients and doctors themselves, MASLD is a growing interdisciplinary problem and a real challenge for modern medicine. The main cause of MASLD is an inappropriate lifestyle-inadequate nutrition and insufficient physical activity, which lead to various components of metabolic syndrome. Lifestyle changes-appropriate diet, weight reduction, and systematic physical activity-are also the basis for the prevention and treatment of MASLD. Hence, in recent years, so much importance has been attached to lifestyle medicine, to non-pharmacological treatment as prevention of lifestyle diseases. The narrative review presents possible therapeutic options for non-pharmacological management in the prevention and treatment of MASLD. The best documented and available diets used in MASLD were discussed, focusing on the benefits and drawbacks of the Mediterranean, high-protein, ketogenic, and intermittent fasting diets. In addition, the most recent recommendations regarding physical activity are summarized.
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Affiliation(s)
- Paweł Rajewski
- Department of Internal and Infectious Diseases, Provincial Infectious Disease Hospital, 85-030 Bydgoszcz, Poland
- Faculty of Health Sciences, University of Health Sciences in Bydgoszcz, 85-067 Bydgoszcz, Poland
| | - Jakub Cieściński
- Department of Radiology, Provincial Infectious Disease Hospital, 85-030 Bydgoszcz, Poland;
| | - Piotr Rajewski
- Department of Neurology, Collegium Medicum—Faculty of Medicine, Nicolaus Copernicus University in Toruń, 85-094 Bygoszcz, Poland;
| | - Szymon Suwała
- Department of Endocrinology and Diabetology, Collegium Medicum—Faculty of Medicine, Nicolaus Copernicus University in Toruń, 85-094 Bydgoszcz, Poland;
| | - Alicja Rajewska
- University Clinical Hospital, 60-355 Poznań, Poland; (A.R.); (M.P.)
| | - Maciej Potasz
- University Clinical Hospital, 60-355 Poznań, Poland; (A.R.); (M.P.)
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2
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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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3
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Zhang C, Hou B, Xu Y, Zeng S, Luo X, Zhang B. Association between eicosapentaenoic acid consumption and the risk of depressive symptoms in US adults: Analyses from NHANES 2005-2018. J Affect Disord 2024; 354:62-67. [PMID: 38479498 DOI: 10.1016/j.jad.2024.03.055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 03/05/2024] [Accepted: 03/09/2024] [Indexed: 04/15/2024]
Abstract
BACKGROUND This study examines the relationship between eicosapentaenoic acid (EPA) intake from food and depression. EPA, an Omega-3 fatty acid commonly found in fish and seafood, has garnered attention for its potential role in depression prevention and treatment. METHODS We selected 30,976 participants from the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2018. Depressive symptoms were diagnosed using the Patient Health Questionnaire (PHQ-9). EPA intake was assessed through dietary evaluation. Logistic regression and restricted cubic spline regression (RCS) were employed to assess the correlation between EPA and depressive symptom. RESULTS The prevalence of depressive symptoms was 7.3 %. Participants with depressive symptoms exhibited lower EPA intake from food compared to non-depressed individuals. This negative association with depressive symptoms persisted even after accounting for various potential influencing factors (e.g., age, gender, body mass index, total energy intake, comorbidities). Notably, EPA demonstrated a nonlinear association with depressive symptoms, particularly in females. CONCLUSIONS This study emphasizes a significant negative correlation between EPA consumption and depressive symptoms, particularly in females. This suggests that maintaining a rich EPA diet may play a role in depression prevention and treatment.
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Affiliation(s)
- Chenxi Zhang
- Department of Psychiatry, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Center of Sleep Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Bingnan Hou
- College of Computer, National University of Defense Technology, Changsha, Hunan, China
| | - Yan Xu
- Department of Psychiatry, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Center of Sleep Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Shufei Zeng
- Department of Psychiatry, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Center of Sleep Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Xue Luo
- Department of Psychiatry, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Center of Sleep Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Bin Zhang
- Department of Psychiatry, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Center of Sleep Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
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Xie X, Liu X, Li R, Fan L, Huang F. ω‑3 fatty acids in atherosclerotic cardiovascular disease (Review). Biomed Rep 2024; 20:94. [PMID: 38765861 PMCID: PMC11099599 DOI: 10.3892/br.2024.1782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 04/11/2024] [Indexed: 05/22/2024] Open
Abstract
Atherosclerotic cardiovascular disease (ASCVD) is one of the most common chronic diseases in the world. Epidemiological evidence and clinical trials have shown that ω-3 fatty acids have a variety of promoting effects in reducing the risk of ASCVD, but different conclusions of large randomized controlled trials make their clinical use in the prevention and treatment of ASCVD controversial. The present review focuses on the pharmacological mechanism, clinical trials and evidence value of clinical applications of ω-3 fatty acids in order to provide theoretical and practical evidence for the clinical application strategy, and follow-up research and development of ω-3 fatty acids as anti-ASCVD drugs.
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Affiliation(s)
- Xingxing Xie
- Department of Pharmacy, Yaan People's Hospital, Yaan, Sichuan 625000, P.R. China
| | - Xue Liu
- Department of Pharmacy, Yaan People's Hospital, Yaan, Sichuan 625000, P.R. China
| | - Rong Li
- Department of Pharmacy, Yaan People's Hospital, Yaan, Sichuan 625000, P.R. China
| | - Ling Fan
- Clinical Trial Center for Drugs and Medical Devices, Yaan People's Hospital, Yaan, Sichuan 625000, P.R. China
| | - Fujing Huang
- Department of Pharmacy, Yaan People's Hospital, Yaan, Sichuan 625000, P.R. China
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El-Sheekh M, Bedaiwy M, Mansour H, El-Shenody RA. Efficiency of the fatty acids extracted from the microalga Parachlorella kessleri in wound-healing. Burns 2024; 50:924-935. [PMID: 38378390 DOI: 10.1016/j.burns.2024.01.019] [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: 06/22/2023] [Revised: 01/13/2024] [Accepted: 01/15/2024] [Indexed: 02/22/2024]
Abstract
Wound healing is a physiological process that results in the reconstruction and restoration of granulation tissue, followed by scar formation. We explored the impact of fatty acids in the form of oils on wound healing since they are part of membrane phospholipids and participate in the inflammatory response. This work investigated the efficiency of fatty acids extracted from microalga Parachlorella kessleri in treating excisional wounds and burns and evaluated their antioxidant activity. The rationale behind this investigation lies in the integral role fatty acids play in membrane phospholipids and their involvement in the inflammatory response. Among different nitrogen sources, glycine showed the highest biomass and lipid productivity (0.08 g L-1 d-1 and 58.37 μgml-1 day-1, respectively). Based on the percentage of polyunsaturated fatty acids that increased by 50.38 % in the Glycine culture of P. kessleri, both total antioxidant capacity and DPPH radical scavenging activity were higher in the Glycine culture than control culture. In 30 anaesthetized male mice divided into 6 groups, using either a burn or an excision, two identical paravertebral full-thickness skin lesions were created. Either oils of P. kessleri (extracted from control and glycine culture) ointments or the vehicle (placebo cream) were applied twice daily to the excisional wounds of mice, while mebo cream was used for burn wounds as well as P. kessleri oil. P. kessleri oils (control or glycine culture) showed a significant effect on the reduction of excisional wounds and burns. Histopathological analysis showed that angiogenesis, collagen fiber formation, and epidermis creation were some of the healing indicators that improved. The key elements for this healing property are omega -3 fatty acids, and both P. kessleri oils extracted from control and glycine culture have significant wound-healing effects. Oil of glycine culture of P. kessleri, however, displayed superior results in this regard.
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Affiliation(s)
- Mostafa El-Sheekh
- Botany Department, Faculty of Science, Tanta University, Tanta 31527, Egypt.
| | - Mohamed Bedaiwy
- Botany Department, Faculty of Science, Tanta University, Tanta 31527, Egypt
| | - Heba Mansour
- Botany Department, Faculty of Science, Tanta University, Tanta 31527, Egypt
| | - Rania A El-Shenody
- Botany Department, Faculty of Science, Tanta University, Tanta 31527, Egypt
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Das UN. Can essential fatty acids (EFAs) prevent and ameliorate post-COVID-19 long haul manifestations? Lipids Health Dis 2024; 23:112. [PMID: 38641607 PMCID: PMC11027247 DOI: 10.1186/s12944-024-02090-4] [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: 01/17/2024] [Accepted: 03/25/2024] [Indexed: 04/21/2024] Open
Abstract
It is hypothesized that COVID-19, post-COVID and post-mRNA COVID-19 (and other related) vaccine manifestations including "long haul syndrome" are due to deficiency of essential fatty acids (EFAs) and dysregulation of their metabolism. This proposal is based on the observation that EFAs and their metabolites can modulate the swift immunostimulatory response of SARS-CoV-2 and similar enveloped viruses, suppress inappropriate cytokine release, possess cytoprotective action, modulate serotonin and bradykinin production and other neurotransmitters, inhibit NF-kB activation, regulate cGAS-STING pathway, modulate gut microbiota, inhibit platelet activation, regulate macrophage and leukocyte function, enhance wound healing and facilitate tissue regeneration and restore homeostasis. This implies that administration of EFAs could be of benefit in the prevention and management of COVID-19 and its associated complications.
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Affiliation(s)
- Undurti N Das
- UND Life Sciences, 2221 NW 5th St, Battle ground, WA, 98604, USA.
- Department of Biotechnology, Indian Institute of Technology-Hyderabad, Sangareddy, Telangana, India.
- Department of Immunology and Rheumatology, Arete Hospitals, Gachibowli, Hyderabad, 4500032, India.
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7
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Erazo-Oliveras A, Muñoz-Vega M, Salinas ML, Wang X, Chapkin RS. Dysregulation of cellular membrane homeostasis as a crucial modulator of cancer risk. FEBS J 2024; 291:1299-1352. [PMID: 36282100 PMCID: PMC10126207 DOI: 10.1111/febs.16665] [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: 06/18/2022] [Revised: 09/09/2022] [Accepted: 10/24/2022] [Indexed: 11/07/2022]
Abstract
Cellular membranes serve as an epicentre combining extracellular and cytosolic components with membranous effectors, which together support numerous fundamental cellular signalling pathways that mediate biological responses. To execute their functions, membrane proteins, lipids and carbohydrates arrange, in a highly coordinated manner, into well-defined assemblies displaying diverse biological and biophysical characteristics that modulate several signalling events. The loss of membrane homeostasis can trigger oncogenic signalling. More recently, it has been documented that select membrane active dietaries (MADs) can reshape biological membranes and subsequently decrease cancer risk. In this review, we emphasize the significance of membrane domain structure, organization and their signalling functionalities as well as how loss of membrane homeostasis can steer aberrant signalling. Moreover, we describe in detail the complexities associated with the examination of these membrane domains and their association with cancer. Finally, we summarize the current literature on MADs and their effects on cellular membranes, including various mechanisms of dietary chemoprevention/interception and the functional links between nutritional bioactives, membrane homeostasis and cancer biology.
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Affiliation(s)
- Alfredo Erazo-Oliveras
- Program in Integrative Nutrition and Complex Diseases; Texas A&M University; College Station, Texas, 77843; USA
- Department of Nutrition; Texas A&M University; College Station, Texas, 77843; USA
| | - Mónica Muñoz-Vega
- Program in Integrative Nutrition and Complex Diseases; Texas A&M University; College Station, Texas, 77843; USA
- Department of Nutrition; Texas A&M University; College Station, Texas, 77843; USA
| | - Michael L. Salinas
- Program in Integrative Nutrition and Complex Diseases; Texas A&M University; College Station, Texas, 77843; USA
- Department of Nutrition; Texas A&M University; College Station, Texas, 77843; USA
| | - Xiaoli Wang
- Program in Integrative Nutrition and Complex Diseases; Texas A&M University; College Station, Texas, 77843; USA
- Department of Nutrition; Texas A&M University; College Station, Texas, 77843; USA
| | - Robert S. Chapkin
- Program in Integrative Nutrition and Complex Diseases; Texas A&M University; College Station, Texas, 77843; USA
- Department of Nutrition; Texas A&M University; College Station, Texas, 77843; USA
- Center for Environmental Health Research; Texas A&M University; College Station, Texas, 77843; USA
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Lewis JI, Lind MV, Møller G, Hansen T, Pedersen H, Christensen MMB, Laursen JC, Nielsen S, Ottendahl CB, Larsen CVL, Stark KD, Bjerregaard P, Jørgensen ME, Lauritzen L. The effect of traditional diet on glucose homoeostasis in carriers and non-carriers of a common TBC1D4 variant in Greenlandic Inuit: a randomised crossover study. Br J Nutr 2023; 130:1871-1884. [PMID: 37129117 PMCID: PMC10632723 DOI: 10.1017/s000711452300106x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 04/07/2023] [Accepted: 04/24/2023] [Indexed: 05/03/2023]
Abstract
Consumption of traditional foods is decreasing amid a lifestyle transition in Greenland as incidence of type 2 diabetes (T2D) increases. In homozygous carriers of a TBC1D4 variant, conferring postprandial insulin resistance, the risk of T2D is markedly higher. We investigated the effects of traditional marine diets on glucose homoeostasis and cardio-metabolic health in Greenlandic Inuit carriers and non-carriers of the variant in a randomised crossover study consisting of two 4-week dietary interventions: Traditional (marine-based, low-carbohydrate) and Western (high in imported meats and carbohydrates). Oral glucose tolerance test (OGTT, 2-h), 14-d continuous glucose and cardio-metabolic markers were assessed to investigate the effect of diet and genotype. Compared with the Western diet, the Traditional diet reduced mean and maximum daily blood glucose by 0·17 mmol/l (95 % CI 0·05, 0·29; P = 0·006) and 0·26 mmol/l (95 % CI 0·06, 0·46; P = 0·010), respectively, with dose-dependency. Furthermore, it gave rise to a weight loss of 0·5 kg (95 % CI; 0·09, 0·90; P = 0·016) relative to the Western diet and 4 % (95 % CI 1, 9; P = 0·018) lower LDL:HDL-cholesterol, which after adjustment for weight loss appeared to be driven by HDL elevation (0·09 mmol/l (0·03, 0·15), P = 0·006). A diet-gene interaction was indicated on insulin sensitivity in the OGTT (p = 0·093), which reflected a non-significant increase of 1·4 (-0·6, 3·5) mmol/l in carrier 2-h glucose. A Traditional diet marginally improved daily glycaemic control and plasma lipid profile compared with a Westernised diet in Greenlandic Inuit. Possible adverse effects on glucose tolerance in carriers of the TBC1D4 variant warrant further studies.
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Affiliation(s)
- Jack Ivor Lewis
- Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
| | - Mads Vendelbo Lind
- Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
| | - Grith Møller
- Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
| | - Torben Hansen
- The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | | | | | | | - Sara Nielsen
- Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
| | | | | | - Ken D. Stark
- Department of Kinesiology and Health Sciences, University of Waterloo, Waterloo, Canada
| | - Peter Bjerregaard
- National Institute of Public Health, University of Southern Denmark, Odense, Denmark
- SDU, Copenhagen, Denmark
| | - Marit E. Jørgensen
- Steno Diabetes Center Copenhagen, Gentofte, Denmark
- Ilisimatusarfik, The University of Greenland, Nuuk, Greenland
| | - Lotte Lauritzen
- Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
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Guriec N, Le Foll C, Delarue J. Long-chain n-3 PUFA given before and throughout gestation and lactation in rats prevent high-fat diet-induced insulin resistance in male offspring in a tissue-specific manner. Br J Nutr 2023; 130:1121-1136. [PMID: 36688295 DOI: 10.1017/s000711452300017x] [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: 01/24/2023]
Abstract
This study investigated whether long-chain n-3 PUFA (LC n-3 PUFA) given to pregnant rats fed a high-fat (HF) diet may prevent fetal programming in male offspring at adulthood. Six weeks before mating, and throughout gestation and lactation, female nulliparous Sprague-Dawley rats were given a chow (C) diet, HF (60·6 % fat from maize, rapeseed oils and lard) or HF in which one-third of fat was replaced by fish oil (HF n-3). At weaning, the three offspring groups were randomly separated in two groups fed C diet, or HF without LC n-3 PUFA, for 7 weeks until adulthood. Glucose tolerance and insulin sensitivity were assessed by an oral glucose tolerance test both at weaning and at adulthood. Insulin signalling was determined in liver, muscle and adipose tissue by quantification of the phosphorylation of Akt on Ser 473 at adulthood. At weaning, as at adulthood, offspring from HF-fed dams were obese and displayed glucose intolerance (GI) and insulin resistance (IR), but not those from HFn-3 fed dams. Following the post-weaning C diet, phosphorylation of Akt was strongly reduced in all tissues of offspring from HF dams, but to a lesser extent in liver and muscle of offspring from HFn-3 dams. However, it was abolished in all tissues of all offspring groups fed the HF post-weaning diet. Thus, LC n-3 PUFA introduced in a HF in dams partially prevented the transmission of GI and IR in adult offspring even though they were fed without LC n-3 PUFA from weaning.
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Affiliation(s)
- Nathalie Guriec
- Department of Nutritional Sciences, University Hospital/Faculty of Medicine/University of Brest, Brest, France
| | - Christelle Le Foll
- Department of Nutritional Sciences, University Hospital/Faculty of Medicine/University of Brest, Brest, France
| | - Jacques Delarue
- Department of Nutritional Sciences, University Hospital/Faculty of Medicine/University of Brest, Brest, France
- ER 7479 SPURBO, University Hospital/Faculty of Medicine/University of Brest, Brest, France
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10
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Emad NA, Sultana Y, Aqil M, Saleh A, Al kamaly O, Nasr FA. Omega-3 fatty acid-based self-microemulsifying drug delivery system (SMEDDS) of pioglitazone: Optimization, in vitro and in vivo studies. Saudi J Biol Sci 2023; 30:103778. [PMID: 37663396 PMCID: PMC10470285 DOI: 10.1016/j.sjbs.2023.103778] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 08/02/2023] [Accepted: 08/10/2023] [Indexed: 09/05/2023] Open
Abstract
Pioglitazone (PGL) is an effective insulin sensitizer, however, side effects such as accumulation of subcutaneous fat, edema, and weight gain as well as poor oral bioavailability limit its therapeutic potential for oral delivery. Recent studies have shown that combination of both, PGL and fish oil significantly reduce fasting plasma glucose, improve insulin resistance, and mitigate pioglitazone-induced subcutaneous fat accumulation and weight gain. Nevertheless, developing an effective oral drug delivery system for administration of both medications have not been explored yet. Thus, this study aimed to develop a self-micro emulsifying drug delivery system (SMEDDS) for the simultaneous oral administration of PGL and fish oil. SMEDDS was developed using concentrated fish oil,Tween® 80, and Transcutol HP and optimized by central composite design (CCD). The reconstituted, optimized PGL-SMEDDS exhibited a globule size of 142 nm, a PDI of 0.232, and a zeta potential of -20.9 mV. The in-vitro drug release study of the PGL-SMEDDS showed a first-order model kinetic release and demonstrated remarkable 15-fold enhancement compared to PGL suspension. Additionally, following oral administration in fasting albino Wistar rats, PGL-SMEDDS exhibited 3.4-fold and 1.4-fold enhancements in the AUC0-24h compared to PGL suspension and PGL marketed product. The accelerated stability testing showed that the optimized SMEDDS formulation was stable over a three-month storage period. Taken together, our findings demonstrate that the developed fish oil-based SMEDDS for PGL could serve as effective nanoplatforms for the oral delivery of PGL, warranting future studies to explore its synergistic therapeutic potential in rats.
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Affiliation(s)
- Nasr A. Emad
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard (Deemed University), M. B. Road, New Delhi 110062, India
| | - Yasmin Sultana
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard (Deemed University), M. B. Road, New Delhi 110062, India
| | - Mohd Aqil
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard (Deemed University), M. B. Road, New Delhi 110062, India
| | - Asmaa Saleh
- Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O Box 84428, Riyadh 11671, Saudi Arabia
| | - Omkulthom Al kamaly
- Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O Box 84428, Riyadh 11671, Saudi Arabia
| | - Fahd A Nasr
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
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11
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Nagarajan SR, Livingstone EJ, Monfeuga T, Lewis LC, Ali SHL, Chandran A, Dearlove DJ, Neville MJ, Chen L, Maroteau C, Ruby MA, Hodson L. MLX plays a key role in lipid and glucose metabolism in humans: Evidence from in vitro and in vivo studies. Metabolism 2023; 144:155563. [PMID: 37088121 PMCID: PMC10687193 DOI: 10.1016/j.metabol.2023.155563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 04/13/2023] [Accepted: 04/17/2023] [Indexed: 04/25/2023]
Abstract
BACKGROUND AND AIM Enhanced hepatic de novo lipogenesis (DNL) has been proposed as an underlying mechanism for the development of NAFLD and insulin resistance. Max-like protein factor X (MLX) acts as a heterodimer binding partner for glucose sensing transcription factors and inhibition of MLX or downstream targets has been shown to alleviate intrahepatic triglyceride (IHTG) accumulation in mice. However, its effect on insulin sensitivity remains unclear. As human data is lacking, the aim of the present work was to investigate the role of MLX in regulating lipid and glucose metabolism in primary human hepatocytes (PHH) and in healthy participants with and without MLX polymorphisms. METHODS PHH were transfected with non-targeting or MLX siRNA to assess the effect of MLX knockdown on lipid and glucose metabolism, insulin signalling and the hepatocellular transcriptome. A targeted association analysis on imputed genotype data for MLX on healthy individuals was undertaken to assess associations between specific MLX SNPs (rs665268, rs632758 and rs1474040), plasma biochemistry, IHTG content, DNL and gluconeogenesis. RESULTS MLX knockdown in PHH altered lipid metabolism (decreased DNL (p < 0.05), increased fatty acid oxidation and ketogenesis (p < 0.05), and reduced lipid accumulation (p < 0.001)). Additionally, MLX knockdown increased glycolysis, lactate secretion and glucose production (p < 0.001) and insulin-stimulated pAKT levels (p < 0.01) as assessed by transcriptomic, steady-state and dynamic measurements. Consistent with the in vitro data, individuals with the rs1474040-A and rs632758-C variants had lower fasting plasma insulin (p < 0.05 and p < 0.01, respectively) and TG (p < 0.05 and p < 0.01, respectively). Although there was no difference in IHTG or gluconeogenesis, individuals with rs632758 SNP had notably lower hepatic DNL (p < 0.01). CONCLUSION We have demonstrated using human in vitro and in vivo models that MLX inhibition favored lipid catabolism over anabolism and increased glucose production, despite increased glycolysis and phosphorylation of Akt, suggesting a metabolic mechanism that involves futile cycling.
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Affiliation(s)
- Shilpa R Nagarajan
- Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford, UK
| | | | - Thomas Monfeuga
- Novo Nordisk Research Centre Oxford, Innovation Building, Oxford, UK
| | - Lara C Lewis
- Novo Nordisk Research Centre Oxford, Innovation Building, Oxford, UK
| | | | | | - David J Dearlove
- Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford, UK
| | - Matt J Neville
- Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford, UK; National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospital Trusts, UK
| | - Lingyan Chen
- Novo Nordisk Research Centre Oxford, Innovation Building, Oxford, UK
| | - Cyrielle Maroteau
- Novo Nordisk Research Centre Oxford, Innovation Building, Oxford, UK
| | - Maxwell A Ruby
- Novo Nordisk Research Centre Oxford, Innovation Building, Oxford, UK.
| | - Leanne Hodson
- Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford, UK; National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospital Trusts, UK.
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Westra J, Annevelink C, Orchard T, Hou L, Harris WS, O'Connell TD, Shearer G, Tintle N. Genome-wide association study of Red Blood Cell fatty acids in the Women's Health Initiative Memory Study. Prostaglandins Leukot Essent Fatty Acids 2023; 194:102577. [PMID: 37285607 PMCID: PMC10320552 DOI: 10.1016/j.plefa.2023.102577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 05/25/2023] [Accepted: 05/31/2023] [Indexed: 06/09/2023]
Abstract
Despite their widespread associations with a wide variety of disease phenotypes, the genetics of red blood cell fatty acids remains understudied. We present one of the first genome-wide association studies of red blood cell fatty acid levels, using the Women's Health Initiative Memory study - a prospective cohort of N = 7,479 women aged 65-79. Approximately 9 million SNPs were measured directly or imputed and, in separate linear models adjusted for age and genetic principal components of ethnicity, SNPs were used to predict 28 different fatty acids. SNPs were considered genome-wide significant using a standard genome-wide significance level of p < 1 × 10-8. Twelve separate loci were identified, seven of which replicated results of a prior RBC-FA GWAS. Of the five novel loci, two have functional annotations directly related to fatty acids (ELOVL6 and ACSL6). While overall explained variation is low, the twelve loci identified provide strong evidence of direct relationships between these genes and fatty acid levels. Further studies are needed to establish and confirm the biological mechanisms by which these genes may directly contribute to fatty acid levels.
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Affiliation(s)
- Jason Westra
- Fatty Acid Research Institute, Sioux Falls, SD, United States of America
| | - Carmen Annevelink
- Department of Nutrition, Penn State University, State College, PA, United States of America
| | - Tonya Orchard
- Human Nutrition Program, Department of Human Sciences, Ohio State University, Columbus, OH, United States of America
| | - Lifang Hou
- Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America
| | - William S Harris
- Fatty Acid Research Institute, Sioux Falls, SD, United States of America; Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, United States of America
| | - Timothy D O'Connell
- Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN, United States of America
| | - Gregory Shearer
- Department of Nutrition, Penn State University, State College, PA, United States of America
| | - Nathan Tintle
- Fatty Acid Research Institute, Sioux Falls, SD, United States of America; Department of Population Health Nursing Science, College of Nursing, University of Illinois - Chicago, Chicago, IL, United States of America.
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Strandvik B, Qureshi AR, Painer J, Backman-Johansson C, Engvall M, Fröbert O, Kindberg J, Stenvinkel P, Giroud S. Elevated plasma phospholipid n-3 docosapentaenoic acid concentrations during hibernation. PLoS One 2023; 18:e0285782. [PMID: 37294822 PMCID: PMC10256182 DOI: 10.1371/journal.pone.0285782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Accepted: 04/28/2023] [Indexed: 06/11/2023] Open
Abstract
Factors for initiating hibernation are unknown, but the condition shares some metabolic similarities with consciousness/sleep, which has been associated with n-3 fatty acids in humans. We investigated plasma phospholipid fatty acid profiles during hibernation and summer in free-ranging brown bears (Ursus arctos) and in captive garden dormice (Eliomys quercinus) contrasting in their hibernation patterns. The dormice received three different dietary fatty acid concentrations of linoleic acid (LA) (19%, 36% and 53%), with correspondingly decreased alpha-linolenic acid (ALA) (32%, 17% and 1.4%). Saturated and monounsaturated fatty acids showed small differences between summer and hibernation in both species. The dormice diet influenced n-6 fatty acids and eicosapentaenoic acid (EPA) concentrations in plasma phospholipids. Consistent differences between summer and hibernation in bears and dormice were decreased ALA and EPA and marked increase of n-3 docosapentaenoic acid and a minor increase of docosahexaenoic acid in parallel with several hundred percent increase of the activity index of elongase ELOVL2 transforming C20-22 fatty acids. The highest LA supply was unexpectantly associated with the highest transformation of the n-3 fatty acids. Similar fatty acid patterns in two contrasting hibernating species indicates a link to the hibernation phenotype and requires further studies in relation to consciousness and metabolism.
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Affiliation(s)
- Birgitta Strandvik
- Department of Biosciences and Nutrition, Karolinska Institutet NEO, Stockholm, Sweden
| | | | - Johanna Painer
- Research Institute of Wildlife Ecology, Department of Interdisciplinary Life Sciences, University of Veterinary Medicine, Vienna, Austria
| | | | - Martin Engvall
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - Ole Fröbert
- Department of Cardiology, Faculty of Health, Örebro University, Örebro, Sweden
- Department of Clinical Medicine, Aarhus University Health, Aarhus, Denmark
- Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark
- StenoDiabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
| | - Jonas Kindberg
- Department of Wildlife, Fish and Environmental Studies, University of Agricultural Sciences, Umeå, Sweden
- Norwegian Institute for Nature Research, Trondheim, Norway
| | - Peter Stenvinkel
- Division of Renal Medicine, CLINTEC, Karolinska Institutet, Stockholm, Sweden
| | - Sylvain Giroud
- Research Institute of Wildlife Ecology, Department of Interdisciplinary Life Sciences, University of Veterinary Medicine, Vienna, Austria
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Sundrani D, Karkhanis A, Randhir K, Panchanadikar T, Joshi S. MicroRNAs targeting peroxisome proliferator-activated receptor (PPAR) gene are differentially expressed in low birth weight placentae. Placenta 2023; 139:51-60. [PMID: 37311266 DOI: 10.1016/j.placenta.2023.06.006] [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: 01/29/2023] [Revised: 05/23/2023] [Accepted: 06/07/2023] [Indexed: 06/15/2023]
Abstract
INTRODUCTION Peroxisome proliferator-activated receptors (PPARs) are activated by natural ligands like fatty acids and influence placental angiogenesis and pregnancy outcome. However, the underlying molecular mechanisms are not clear. This study aims to investigate the association of maternal and placental fatty acid levels with DNA methylation and microRNA regulation of PPARs in the placentae of women delivering low birth weight (LBW) babies. METHODS This study includes 100 women delivering normal birth weight (NBW) baby and 70 women delivering LBW baby. Maternal and placental fatty acids levels were estimated by gas chromatograph. Gene promoter methylation and mRNA expression of PPARs was analyzed using Epitect Methyl-II PCR assay kit and RT-PCR respectively. Expression of miRNAs targeting PPAR mRNA were analyzed using a Qiagen miRCURY LNA PCR Array on RT-PCR. RESULTS Placental docosahexaenoic acid (DHA) levels and placental mRNA expression of PPARα and PPARγ were lower (p < 0.05 for all) in the LBW group. Differential expression of miRNAs (upregulated miR-33a-5p and miR-22-5p; downregulated miR-301a-5p, miR-518d-5p, miR-27b-5p, miR-106a-5p, miR-21-5p, miR-548d-5p, miR-17-5p and miR-20a-5p) (p < 0.05 for all) was observed in the LBW group. Maternal and placental polyunsaturated fatty acids and total omega-3 fatty acids were positively associated while saturated fatty acids were negatively associated with expression of miRNAs (p < 0.05 for all). Placental expression of miRNAs were positively associated with birth weight (p < 0.05 for all). DISCUSSION Our data suggests that maternal fatty acid status is associated with changes in the placental expression of miRNAs targeting PPAR gene in women delivering LBW babies.
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Affiliation(s)
- Deepali Sundrani
- Mother and Child Health, Interactive Research School for Health Affairs, Bharati Vidyapeeth (Deemed to be University), Pune, 411043, India.
| | - Aishwarya Karkhanis
- Mother and Child Health, Interactive Research School for Health Affairs, Bharati Vidyapeeth (Deemed to be University), Pune, 411043, India
| | - Karuna Randhir
- Mother and Child Health, Interactive Research School for Health Affairs, Bharati Vidyapeeth (Deemed to be University), Pune, 411043, India
| | - Tushar Panchanadikar
- Department of Obstetrics and Gynecology, Bharati Medical College and Hospital, Bharati Vidyapeeth (Deemed to be University), Pune, 411043, India
| | - Sadhana Joshi
- Mother and Child Health, Interactive Research School for Health Affairs, Bharati Vidyapeeth (Deemed to be University), Pune, 411043, India
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Brosolo G, Da Porto A, Marcante S, Picci A, Capilupi F, Capilupi P, Bertin N, Vivarelli C, Bulfone L, Vacca A, Catena C, Sechi LA. Omega-3 Fatty Acids in Arterial Hypertension: Is There Any Good News? Int J Mol Sci 2023; 24:9520. [PMID: 37298468 PMCID: PMC10253816 DOI: 10.3390/ijms24119520] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 05/28/2023] [Accepted: 05/29/2023] [Indexed: 06/12/2023] Open
Abstract
Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), including alpha-linolenic acid (ALA) and its derivatives eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are "essential" fatty acids mainly obtained from diet sources comprising plant oils, marine blue fish, and commercially available fish oil supplements. Many epidemiological and retrospective studies suggested that ω-3 PUFA consumption decreases the risk of cardiovascular disease, but results of early intervention trials have not consistently confirmed this effect. In recent years, some large-scale randomized controlled trials have shed new light on the potential role of ω-3 PUFAs, particularly high-dose EPA-only formulations, in cardiovascular prevention, making them an attractive tool for the treatment of "residual" cardiovascular risk. ω-3 PUFAs' beneficial effects on cardiovascular outcomes go far beyond the reduction in triglyceride levels and are thought to be mediated by their broadly documented "pleiotropic" actions, most of which are directed to vascular protection. A considerable number of clinical studies and meta-analyses suggest the beneficial effects of ω-3 PUFAs in the regulation of blood pressure in hypertensive and normotensive subjects. These effects occur mostly through regulation of the vascular tone that could be mediated by both endothelium-dependent and independent mechanisms. In this narrative review, we summarize the results of both experimental and clinical studies that evaluated the effect of ω-3 PUFAs on blood pressure, highlighting the mechanisms of their action on the vascular system and their possible impact on hypertension, hypertension-related vascular damage, and, ultimately, cardiovascular outcomes.
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Affiliation(s)
- Gabriele Brosolo
- Department of Medicine, University of Udine, 33100 Udine, Italy; (A.D.P.); (S.M.); (A.P.); (F.C.); (P.C.); (N.B.); (C.V.); (L.B.); (A.V.); (C.C.)
- European Hypertension Excellence Center, Clinica Medica, University of Udine, 33100 Udine, Italy
| | - Andrea Da Porto
- Department of Medicine, University of Udine, 33100 Udine, Italy; (A.D.P.); (S.M.); (A.P.); (F.C.); (P.C.); (N.B.); (C.V.); (L.B.); (A.V.); (C.C.)
- Diabetes and Metabolism Unit, Clinica Medica, University of Udine, 33100 Udine, Italy
| | - Stefano Marcante
- Department of Medicine, University of Udine, 33100 Udine, Italy; (A.D.P.); (S.M.); (A.P.); (F.C.); (P.C.); (N.B.); (C.V.); (L.B.); (A.V.); (C.C.)
| | - Alessandro Picci
- Department of Medicine, University of Udine, 33100 Udine, Italy; (A.D.P.); (S.M.); (A.P.); (F.C.); (P.C.); (N.B.); (C.V.); (L.B.); (A.V.); (C.C.)
| | - Filippo Capilupi
- Department of Medicine, University of Udine, 33100 Udine, Italy; (A.D.P.); (S.M.); (A.P.); (F.C.); (P.C.); (N.B.); (C.V.); (L.B.); (A.V.); (C.C.)
| | - Patrizio Capilupi
- Department of Medicine, University of Udine, 33100 Udine, Italy; (A.D.P.); (S.M.); (A.P.); (F.C.); (P.C.); (N.B.); (C.V.); (L.B.); (A.V.); (C.C.)
| | - Nicole Bertin
- Department of Medicine, University of Udine, 33100 Udine, Italy; (A.D.P.); (S.M.); (A.P.); (F.C.); (P.C.); (N.B.); (C.V.); (L.B.); (A.V.); (C.C.)
- Thrombosis and Hemostasis Unit, Clinica Medica, University of Udine, 33100 Udine, Italy
| | - Cinzia Vivarelli
- Department of Medicine, University of Udine, 33100 Udine, Italy; (A.D.P.); (S.M.); (A.P.); (F.C.); (P.C.); (N.B.); (C.V.); (L.B.); (A.V.); (C.C.)
| | - Luca Bulfone
- Department of Medicine, University of Udine, 33100 Udine, Italy; (A.D.P.); (S.M.); (A.P.); (F.C.); (P.C.); (N.B.); (C.V.); (L.B.); (A.V.); (C.C.)
- European Hypertension Excellence Center, Clinica Medica, University of Udine, 33100 Udine, Italy
| | - Antonio Vacca
- Department of Medicine, University of Udine, 33100 Udine, Italy; (A.D.P.); (S.M.); (A.P.); (F.C.); (P.C.); (N.B.); (C.V.); (L.B.); (A.V.); (C.C.)
- European Hypertension Excellence Center, Clinica Medica, University of Udine, 33100 Udine, Italy
| | - Cristiana Catena
- Department of Medicine, University of Udine, 33100 Udine, Italy; (A.D.P.); (S.M.); (A.P.); (F.C.); (P.C.); (N.B.); (C.V.); (L.B.); (A.V.); (C.C.)
- European Hypertension Excellence Center, Clinica Medica, University of Udine, 33100 Udine, Italy
| | - Leonardo A. Sechi
- Department of Medicine, University of Udine, 33100 Udine, Italy; (A.D.P.); (S.M.); (A.P.); (F.C.); (P.C.); (N.B.); (C.V.); (L.B.); (A.V.); (C.C.)
- European Hypertension Excellence Center, Clinica Medica, University of Udine, 33100 Udine, Italy
- Diabetes and Metabolism Unit, Clinica Medica, University of Udine, 33100 Udine, Italy
- Thrombosis and Hemostasis Unit, Clinica Medica, University of Udine, 33100 Udine, Italy
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Chen Q, Deng X, Zhang K, Kang Y, Jiao M, Zhang J, Wang C, Li F. Changes to PUFA-PPAR pathway during mesaconitine induced myocardial coagulative necrosis. Food Chem Toxicol 2023; 177:113831. [PMID: 37182599 DOI: 10.1016/j.fct.2023.113831] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 05/10/2023] [Accepted: 05/11/2023] [Indexed: 05/16/2023]
Abstract
Coagulation necrosis is characterized by the denaturation of structural proteins and lysosomal enzymes; its occurrence in myocardium can lead to heart failure. Current studies on myocardial injury primarily focus on inflammation, hypertrophy, and hemorrhage, while those on myocardial coagulation necrosis are still limited. Mesaconitine (MA), a C19 diester diterpenoid alkaloid derived from Aconitum carmichaelii Debx, has strong cardiotoxicity. During this study, the myocardial cells of SD rats showed significant coagulative necrosis after 6 days of oral administration of MA at a dose of 1.2 mg/kg/day. Investigations of its biological mechanism showed abnormal levels of polyunsaturated fatty acids (PUFAs) and Peroxisome proliferator activated receptors Alpha (PPARα) pathway related protein. Moreover, MA affected the PPARα signaling pathway through interactions with proteins such as POR, TFAM and GPD1, indirectly indicating that these above proteins are important targets for blocking myocardial coagulative necrosis. This study thus discusses the effects of the use of cardiotoxic compound, MA, to initiate myocardial coagulative necrosis and its associated toxic mechanisms.
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Affiliation(s)
- Qian Chen
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing, 102488, China.
| | - Xinqi Deng
- School of Life Sciences, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing, 102488, China.
| | - Kai Zhang
- School of Life Sciences, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing, 102488, China.
| | - Yingquan Kang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing, 102488, China.
| | - Mingjie Jiao
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing, 102488, China.
| | - Jia Zhang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing, 102488, China.
| | - Chunguo Wang
- Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing, 102488, China.
| | - Fei Li
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing, 102488, China.
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Roszkos R, Tóth T, Bazar G, Fébel H, Mézes M. Effect of omega-3 polyunsaturated fatty acid supplementation on oxidative stress parameters and sex hormone levels of modern genotype sows. Vet Med Sci 2022; 9:191-202. [PMID: 36508581 PMCID: PMC9856994 DOI: 10.1002/vms3.1026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Sows are exposed to severe stress and hormonal challenges during their whole productive life. As polyunsaturated fatty acids play an important role in immune and reproductive functions, with a better understanding of their role in breeding sows' nutrition, improved performance and more sustainable pig production can be achieved. OBJECTIVES In this study, we investigated the effects of omega-6 and omega-3 fatty acid supplementation on the antioxidant status and hormone levels of sows. METHODS A total of 48 Danish Large white × Danish Landrace sows were supplemented either with sunflower oil (SO) as a control group or with fish oil (FO) as experimental group at the same dose of 10 g/kg feed. Blood samples were collected on day 14 of lactation, 5 days after weaning (insemination), and 30 days after insemination. To estimate antioxidant and reproductive effects, the amounts of reduced glutathione (GSH), thiobarbituric acid reactive substance, the activity of glutathione peroxidase (GPx), serum 17β oestradiol (E2), progesterone (P4), and 6-keto prostaglandin F1α (6-keto PGF1α) levels were investigated. RESULTS FO-based supplementation increased GPx activity on day 14 of lactation. Five days after weaning, the concentration of GSH in FO-fed sows was significantly higher than that in SO-fed sows. The E2 content of blood was significantly lower in the experimental group than in the control group for two of the three examined periods (day 14 of lactation and 30 days after insemination), whereas P4 levels were significantly higher in the experimental group 5 days after weaning. We found that 6-keto PGF1α levels were systematically lower in the experimental group throughout the trial. CONCLUSIONS This study provides evidence of the major impact of omega-6 and -3 fatty acids on the tested hormone levels, which serve as precursors for the production of E2 and P4 but have an opposite effect on PGF2α production.
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Affiliation(s)
- Róbert Roszkos
- Department of Feed SafetyInstitute of Physiology and NutritionHungarian University of Agriculture and Life SciencesGödöllőHungary
| | - Tamás Tóth
- ADEXGO Ltd.BalatonfüredHungary,Agricultural and Food Research CentreSzéchenyi István UniversityGyőrHungary
| | | | - Hedvig Fébel
- Nutrition Physiology Research GroupInstitute of Physiology and NutritionHungarian University of Agriculture and Life SciencesHerceghalomHungary
| | - Miklós Mézes
- Department of Feed SafetyInstitute of Physiology and NutritionHungarian University of Agriculture and Life SciencesGödöllőHungary
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Hjorth M, Doncheva A, Norheim F, Ulven SM, Holven KB, Sæther T, Dalen KT. Consumption of salmon fishmeal increases hepatic cholesterol content in obese C57BL/6 J mice. Eur J Nutr 2022; 61:4027-4043. [PMID: 35788891 PMCID: PMC9596588 DOI: 10.1007/s00394-022-02930-y] [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] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 05/31/2022] [Indexed: 12/04/2022]
Abstract
PURPOSE By-products from farmed fish contain large amounts of proteins and may be used for human consumption. The purpose of this study was to investigate cardiometabolic effects and metabolic tolerance in mice consuming fishmeal from salmon by-products, salmon filet or beef. METHODS Female C57BL/6J mice were fed chow, as a healthy reference group, or a high-fat diet for 10 weeks to induce obesity and glucose intolerance. Obese mice were subsequently given isocaloric diets containing 50% of the dietary protein from salmon fishmeal, salmon filet or beef for 10 weeks. Mice were subjected to metabolic phenotyping, which included measurements of body composition, energy metabolism in metabolic cages and glucose tolerance. Lipid content and markers of hepatic toxicity were determined in plasma and liver. Hepatic gene and protein expression was determined with RNA sequencing and immunoblotting. RESULTS Mice fed fishmeal, salmon filet or beef had similar food intake, energy consumption, body weight gain, adiposity, glucose tolerance and circulating levels of lipids and hepatic toxicity markers, such as p-ALT and p-AST. Fishmeal increased hepatic cholesterol levels by 35-36% as compared to salmon filet (p = 0.0001) and beef (p = 0.005). This was accompanied by repressed expression of genes involved in steroid and cholesterol metabolism and reduced levels of circulating Pcsk9. CONCLUSION Salmon fishmeal was well tolerated, but increased hepatic cholesterol content. The high cholesterol content in fishmeal may be responsible for the effects on hepatic cholesterol metabolism. Before introducing fishmeal from salmon by-products as a dietary component, it may be advantageous to reduce the cholesterol content in fishmeal.
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Affiliation(s)
- Marit Hjorth
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Sognsvannsveien 9, Domus Medica, Blindern, P.O. Box 1046, 0317, Oslo, Norway
| | - Atanaska Doncheva
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Sognsvannsveien 9, Domus Medica, Blindern, P.O. Box 1046, 0317, Oslo, Norway
| | - Frode Norheim
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Sognsvannsveien 9, Domus Medica, Blindern, P.O. Box 1046, 0317, Oslo, Norway
| | - Stine Marie Ulven
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Sognsvannsveien 9, Domus Medica, Blindern, P.O. Box 1046, 0317, Oslo, Norway
| | - Kirsten Bjørklund Holven
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Sognsvannsveien 9, Domus Medica, Blindern, P.O. Box 1046, 0317, Oslo, Norway
- Norwegian National Advisory Unit On Familial Hypercholesterolemia, Oslo University Hospital, Aker Sykehus, Postboks 4950, 0424, Oslo, Norway
| | - Thomas Sæther
- Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Sognsvannsveien 9, Domus Medica, 0372, Oslo, Norway
| | - Knut Tomas Dalen
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Sognsvannsveien 9, Domus Medica, Blindern, P.O. Box 1046, 0317, Oslo, Norway.
- The Norwegian Transgenic Center, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
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Comparative analysis of muscle nutrient in two types of hybrid bream and native bream. REPRODUCTION AND BREEDING 2022. [DOI: 10.1016/j.repbre.2022.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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Altering Methane Emission, Fatty Acid Composition, and Microbial Profile during In Vitro Ruminant Fermentation by Manipulating Dietary Fatty Acid Ratios. FERMENTATION-BASEL 2022. [DOI: 10.3390/fermentation8070310] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
This study evaluated the effects of different dietary n-6/n-3 polyunsaturated fatty acid (PUFA) ratios on in vitro ruminant fermentation. Methane production, fatty acid composition, and microbial profiles were compared after the in vitro fermentation of rumen fluid collected from cows that had been fed isoenergetic and isoproteic experimental diets at three different n-6/n-3 ratios: 3.04 (HN6, high n-6 source), 2.03 (MN6, medium n-6 source), and 0.8 (LN6, low n-6 source). The fermented rumen fluid pH and total volatile fatty acid (VFA) levels were significantly decreased (p < 0.05) in the HN6 group as compared with those in the MN6 and LN6 groups. Additionally, the HN6 group produced a significantly lower (p < 0.05) proportion of methane than the MN6 group during in vitro fermentation. The MN6 and LN6 groups had significantly increased (p < 0.05) levels of C18:2n6 and C18:3n3 in the fermented rumen fluid, respectively, as compared with the HN6 group. The Chao 1 diversity index value was lower (p < 0.05) in the HN6 group than in the MN6 and LN6 groups. The observed species richness was significantly lower (p < 0.05) in the HN6 group than in the MN6 group. The reduced relative abundances of Lachnospiraceae UCG-006 and Selenomonas in the HN6 group resulted in lower pH and VFA levels (i.e., acetate, propionate, butyrate, and total VFA) during in vitro fermentation. Furthermore, n-6 and n-3 PUFAs were toxic to Butyrivibrio_2 growth, resulting in high levels of incomplete biohydrogenation. Taken together, the study findings suggest that supplementation of high-forage diets with high levels of n-6 PUFAs could reduce methane emissions, whereas both VFA concentration and pH are reduced.
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21
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Liu J, Shi Y, Peng D, Wang L, Yu N, Wang G, Chen W. Salvia miltiorrhiza Bge. (Danshen) in the Treating Non-alcoholic Fatty Liver Disease Based on the Regulator of Metabolic Targets. Front Cardiovasc Med 2022; 9:842980. [PMID: 35528835 PMCID: PMC9072665 DOI: 10.3389/fcvm.2022.842980] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Accepted: 03/28/2022] [Indexed: 12/12/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is rapidly prevalent due to its strong association with increased metabolic syndrome such as cardio- and cerebrovascular disorders and diabetes. Few drugs can meet the growing disease burden of NAFLD. Salvia miltiorrhiza Bge. (Danshen) have been used for over 2,000 years in clinical trials to treat NAFLD and metabolic syndrome disease without clarified defined mechanisms. Metabolic targets restored metabolic homeostasis in patients with NAFLD and improved steatosis by reducing the delivery of metabolic substrates to liver as a promising way. Here we systematic review evidence showing that Danshen against NAFLD through diverse and crossing mechanisms based on metabolic targets. A synopsis of the phytochemistry and pharmacokinetic of Danshen and the mechanisms of metabolic targets regulating the progression of NAFLD is initially provided, followed by the pharmacological activity of Danshen in the management NAFLD. And then, the possible mechanisms of Danshen in the management of NAFLD based on metabolic targets are elucidated. Specifically, the metabolic targets c-Jun N-terminal kinases (JNK), sterol regulatory element-binding protein-1c (SREBP-1c), nuclear translocation carbohydrate response element–binding protein (ChREBP) related with lipid metabolism pathway, and peroxisome proliferator-activated receptors (PPARs), cytochrome P450 (CYP) and the others associated with pleiotropic metabolism will be discussed. Finally, providing a critical assessment of the preclinic and clinic model and the molecular mechanism in NAFLD.
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Affiliation(s)
- Jie Liu
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, China
- Institute of Traditional Chinese Medicine Resources Protection and Development, Anhui Academy of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Traditional Chinese Medicine Decoction Pieces of New Manufacturing Technology, Hefei, China
| | - Yun Shi
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, China
- Institute of Traditional Chinese Medicine Resources Protection and Development, Anhui Academy of Chinese Medicine, Hefei, China
| | - Daiyin Peng
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, China
- Institute of Traditional Chinese Medicine Resources Protection and Development, Anhui Academy of Chinese Medicine, Hefei, China
| | - Lei Wang
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, China
- Anhui Province Key Laboratory of Traditional Chinese Medicine Decoction Pieces of New Manufacturing Technology, Hefei, China
- *Correspondence: Lei Wang,
| | - Nianjun Yu
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, China
- Institute of Traditional Chinese Medicine Resources Protection and Development, Anhui Academy of Chinese Medicine, Hefei, China
| | - Guokai Wang
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, China
- Institute of Traditional Chinese Medicine Resources Protection and Development, Anhui Academy of Chinese Medicine, Hefei, China
| | - Weidong Chen
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, China
- Institute of Traditional Chinese Medicine Resources Protection and Development, Anhui Academy of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Traditional Chinese Medicine Decoction Pieces of New Manufacturing Technology, Hefei, China
- Weidong Chen,
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22
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Oliva ME, Ingaramo P, Vega Joubert MB, Ferreira MDR, D'Alessandro ME. Effects of Salvia hispanica L. (chia) seed on blood coagulation, endothelial dysfunction and liver fibrosis in an experimental model of Metabolic Syndrome. Food Funct 2021; 12:12407-12420. [PMID: 34797360 DOI: 10.1039/d1fo02274a] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
The aim of this study was to analyze blood coagulation, endothelial dysfunction and liver fibrosis in an experimental model of Metabolic Syndrome (MS) induced by chronic administration of a sucrose-rich diet (SRD) and to evaluate the effects of chia seed as a therapeutic strategy. Male Wistar rats were fed with a reference diet (RD) - 6 months - or a SRD - 3 months. Then, the last group was randomly divided into two subgroups. One subgroup continued receiving the SRD for up to 6 months and the other was fed with a SRD where whole chia seed was incorporated as the source of dietary fat for the next 3 months (SRD + CHIA). Results showed that rats fed a SRD for a long period of time develop dyslipidemia, visceral adiposity, insulin resistance, and a hypercoagulable and hypofibrinolytic basal state. Hepatic VCAM-1 (main adhesion molecules involved in endothelial dysfunction) expression was significantly increased. In addition, the SRD group presented hepatic steatosis, a significant increase in interstitial collagen deposition and hydroxyproline content. Liver TGF-β1 (a key cytokine involved in fibrogenesis) levels increased and a negative correlation with PPARα protein mass levels was found. The administration of chia seed for 3 months reversed dyslipidemia, visceral adiposity and insulin resistance. Platelet count, coagulation parameters and plasma fibrinogen levels were normalized. In the liver tissue, VCAM-1 expression, steatosis, interstitial collagen deposition and the hydroxyproline content decreased. TGF-β1 expression was decreased and this was associated with an increase in the PPARα protein levels. The present study showed new aspects in the progression from liver steatosis to fibrosis in dyslipidemic insulin-resistant rats chronically fed a sucrose-rich diet. Chia seed supplementation could be used as a functional food and a potential dietary strategy to prevent or ameliorate disorders related to atherothrombotic cardiovascular events and NASH.
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Affiliation(s)
- María Eugenia Oliva
- Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Ciudad Universitaria, cc242 (3000) Santa Fe, Argentina.
| | - Paola Ingaramo
- Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquímica y Cs. Biológicas, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Santa Fe, Argentina
| | - Michelle Berenice Vega Joubert
- Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Ciudad Universitaria, cc242 (3000) Santa Fe, Argentina.
| | - María Del Rosario Ferreira
- Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Ciudad Universitaria, cc242 (3000) Santa Fe, Argentina.
| | - María Eugenia D'Alessandro
- Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Ciudad Universitaria, cc242 (3000) Santa Fe, Argentina.
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23
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Zhi Y, Sun Y, Jiao Y, Pan C, Wu Z, Liu C, Su J, Zhou J, Shang D, Niu J, Hua R, Yin P. HR-MS Based Untargeted Lipidomics Reveals Characteristic Lipid Signatures of Wilson's Disease. Front Pharmacol 2021; 12:754185. [PMID: 34880754 PMCID: PMC8645799 DOI: 10.3389/fphar.2021.754185] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 11/02/2021] [Indexed: 11/13/2022] Open
Abstract
Background and Aims: The diagnosis of Wilson's disease (WD) is challenging by clinical or genetic criteria. A typical early pathological change of WD is the increased liver lipid deposition and lowered serum triglyceride (TG). Therefore, the contents of serum lipids may provide evidence for screening of biomarkers for WD. Methods: 34 WD patients, 31 WD relatives, and 65 normal controls were enrolled in this study. Serum lipidomics data was acquired by an ultra-high-performance liquid chromatography high-resolution mass spectrometry system, and the data were analyzed by multivariate statistical methods. Results: Of all 510 identified lipids, there are 297 differential lipids between the WD and controls, 378 differential lipids between the relatives and controls, and 119 differential lipids between the patients and relatives. In WD, the abundances of most saturated TG were increased, whereas other unsaturated lipids decreased, including phosphatidylcholine (PC), sphingomyelin (SM), lysophosphatidylcholine (LPC), ceramide (Cer), and phosphatidylserine (PS). We also found many serum lipid species may be used as biomarkers for WD. The areas under the receiver operating characteristic curve (AUC) of PS (35:0), PS (38:5), and PS (34:0) were 0.919, 0.843, and 0.907. The AUCs of TG (38:0) and CerG1 (d42:2) were 0.948 and 0.915 and the AUCs of LPC (17:0) and LPC (15:0) were 0.980 and 0.960, respectively. The lipid biomarker panel exhibits good diagnostic performance for WD. The correlation networks were built among the different groups and the potential mechanisms of differential lipids were discussed. Interestingly, similar lipid profile of WD is also found in their relatives, which indicated the changes may also related to the mutation of the ATP7B gene. Conclusions: Lipid deregulation is another important hallmark of WD besides the deposition of copper. Our lipidomic results provide new insights into the diagnostic and therapeutic targets of WD.
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Affiliation(s)
- Yixiao Zhi
- Clinical Laboratory of Integrative Medicine, First Affiliated Hospital of Dalian Medical University, Dalian, China.,Department of Hepatology, The First Hospital of Jilin University, Changchun, China
| | - Yujiao Sun
- Clinical Laboratory of Integrative Medicine, First Affiliated Hospital of Dalian Medical University, Dalian, China.,Institute of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Yonggeng Jiao
- Department of Anesthesiology Jilin Province FAW General Hospital, Changchun, China
| | - Chen Pan
- Clinical Laboratory of Integrative Medicine, First Affiliated Hospital of Dalian Medical University, Dalian, China.,Department of General Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Zeming Wu
- iPhenome biotechnology Inc. Dalian (Yun Pu Kang), Dalian, China
| | - Chang Liu
- Clinical Laboratory of Integrative Medicine, First Affiliated Hospital of Dalian Medical University, Dalian, China.,Institute of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Jie Su
- Department of Hepatology, The First Hospital of Jilin University, Changchun, China
| | - Jie Zhou
- Department of Hepatology, The First Hospital of Jilin University, Changchun, China
| | - Dong Shang
- Clinical Laboratory of Integrative Medicine, First Affiliated Hospital of Dalian Medical University, Dalian, China.,Department of Hepatology, The First Hospital of Jilin University, Changchun, China.,Department of General Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Junqi Niu
- Department of Hepatology, The First Hospital of Jilin University, Changchun, China
| | - Rui Hua
- Department of Hepatology, The First Hospital of Jilin University, Changchun, China
| | - Peiyuan Yin
- Clinical Laboratory of Integrative Medicine, First Affiliated Hospital of Dalian Medical University, Dalian, China.,Institute of Integrative Medicine, Dalian Medical University, Dalian, China
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24
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Ahluwalia MK. Nutrigenetics and nutrigenomics-A personalized approach to nutrition. ADVANCES IN GENETICS 2021; 108:277-340. [PMID: 34844714 DOI: 10.1016/bs.adgen.2021.08.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
The prevalence of non-communicable diseases has been on an upward trajectory for some time and this puts an enormous burden on the healthcare expenditure. Lifestyle modifications including dietary interventions hold an immense promise to manage and prevent these diseases. Recent advances in genomic research provide evidence that focussing these efforts on individual variations in abilities to metabolize nutrients (nutrigenetics) and exploring the role of dietary compounds on gene expression (nutrigenomics and nutri-epigenomics) can lead to more meaningful personalized dietary strategies to promote optimal health. This chapter aims to provide examples on these gene-diet interactions at multiple levels to support the need of embedding targeted dietary interventions as a way forward to prevent, avoid and manage diseases.
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25
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Monirujjaman M, Pant A, Nelson R, Bathe O, Jacobs R, Mazurak VC. Alterations in hepatic fatty acids reveal depletion of total polyunsaturated fatty acids following irinotecan plus 5-fluorouracil treatment in an animal model of colorectal cancer. Prostaglandins Leukot Essent Fatty Acids 2021; 174:102359. [PMID: 34740033 DOI: 10.1016/j.plefa.2021.102359] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 08/31/2021] [Accepted: 10/20/2021] [Indexed: 12/24/2022]
Abstract
Fatty liver is a side effect of chemotherapy that limits the ability to treat colorectal cancer (CRC) patients in the most effective way. The aim of this study was to determine hepatic fatty acid composition and expression of genes involved in lipid metabolism at two time points following sequential chemotherapy treatment with Irinotecan (CPT-11)+5-fluorouracil (5-FU), agents commonly used to treat human colorectal cancer. Female Fischer 344 rats were provided a semi-purified AIN-76 basal diet with modified fat component. One cycle of chemotherapy consisted of CPT-11+5-FU and was initiated 2 weeks after tumor implantation (D0); a second cycle was given one week later. Two days after each cycle (Day 2 and Day 9), animals were euthanized, and livers collected. Triacylglycerol (TAG) and phospholipid (PL) fractions were isolated using thin layer chromatography and fatty acids (FAs) were quantified using gas chromatography. Expression of 44 lipid metabolism genes were analyzed by qPCR. Total liver TAG level was lowest after the second cycle D0 and D2 (P = 0.05) characterized by lower content of n-6 and n-3 polyunsaturated fatty acids (PUFAs). N-6 PUFAs significantly declined with subsequent treatments. Of 44 genes analyzed, 13 genes were altered with CPT-11+5-FU treatment. Expression of genes VLCAD and DGAT1, involved in fatty acid oxidation as well as DGAT1 in TAG synthesis, were significantly elevated after each cycle, whereas expression of genes ELOVL2 and FADS2, involved in fatty acid elongation and desaturation were significantly lower at D9 compared to D2 and D0 (P < 0.03). Hepatic total TAG PUFA was depleted, and genes involved in pathways of PUFA synthesis were down-regulated by chemotherapy treatment. This observation suggests impediments in lipid metabolism in the liver that could potentially impact peripheral availability of essential fatty acids.
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Affiliation(s)
- Md Monirujjaman
- Department of Agricultural Food and Nutritional Science, 4-126 Li Ka Shing Centre for Health Research Innovation, University of Alberta, Edmonton, AB, T6G 2P5, Canada
| | - Asha Pant
- Department of Agricultural Food and Nutritional Science, 4-126 Li Ka Shing Centre for Health Research Innovation, University of Alberta, Edmonton, AB, T6G 2P5, Canada
| | - Randy Nelson
- Department of Agricultural Food and Nutritional Science, 4-126 Li Ka Shing Centre for Health Research Innovation, University of Alberta, Edmonton, AB, T6G 2P5, Canada
| | - Oliver Bathe
- Department of Surgical Oncology, University of Calgary, Canada
| | - Rene Jacobs
- Department of Agricultural Food and Nutritional Science, 4-126 Li Ka Shing Centre for Health Research Innovation, University of Alberta, Edmonton, AB, T6G 2P5, Canada
| | - Vera C Mazurak
- Department of Agricultural Food and Nutritional Science, 4-126 Li Ka Shing Centre for Health Research Innovation, University of Alberta, Edmonton, AB, T6G 2P5, Canada; Department of Oncology, Cross Cancer Institute, University of Alberta, Canada.
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26
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Zhou N, Du S, Dai Y, Yang F, Li X. ω3PUFAs improve hepatic steatosis in postnatal overfed rats and HepG2 cells by inhibiting acetyl-CoA carboxylase. Food Sci Nutr 2021; 9:5153-5165. [PMID: 34532024 PMCID: PMC8441356 DOI: 10.1002/fsn3.2482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 06/14/2021] [Accepted: 07/07/2021] [Indexed: 11/18/2022] Open
Abstract
Postnatal overfeeding can lead to persistent increases in hepatic lipid synthesis and the risk of nonalcoholic fatty liver disease (NAFLD) in adulthood. The ω3 polyunsaturated fatty acids (ω3PUFAs) exhibit beneficial effects on NAFLD. Here, we employed a rat model and an in vitro HepG2 cell model to investigate whether fish oil (FO) affects hepatic lipid synthesis due to postnatal overfeeding. Male Sprague-Dawley were divided into litter sizes of three (small litters, SLs) or 10 (normal litters, NLs) on postnatal day 3 and were fed standard chow or FO diet beginning on postnatal week 3 to generate NL, SL, NL-FO, and SL-FO groups. The results indicated that the FO diet reduced the postnatal overfeeding-induced body weight gain and NAFLD characteristics (such as serum and liver triglyceride (TG) and hepatic steatosis). In addition, FO restored the expression of hepatic lipid metabolism-related genes (including SCD1, FASN, CPT1, LPL, ACC, and SREBP-1c) in SL-FO rats. Specifically, the activity and expression pattern of ACC were consistent with SREBP-1c. Furthermore, HepG2 cells were treated with oleic acid (OA), followed by eicosapentenoic acid (EPA), with or without SREBP-1c siRNA. The cellular lipid droplets, TG content, and the expression of ACC (by 75%) and SREBP-1c (by 45%) were increased by OA stimulation (p < .05), which was inhibited by EPA treatment. However, the effect of EPA treatment was abolished when SREBP-1c was silenced. In conclusion, ω3PUFAs-rich diet may be an effective way to reverse the developmental programming of hepatic lipid synthesis, at least partially, by inhibiting ACC through modulating SREBP-1c.
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Affiliation(s)
- Nan Zhou
- Department of Child Health CareChildren’s Hospital of Nanjing Medical UniversityNanjingChina
| | - Susu Du
- Department of Child Health CareChildren’s Hospital of Nanjing Medical UniversityNanjingChina
| | - Yanyan Dai
- Department of Child Health CareChildren’s Hospital of Nanjing Medical UniversityNanjingChina
| | - Fan Yang
- Department of Child Health CareChildren’s Hospital of Nanjing Medical UniversityNanjingChina
| | - Xiaonan Li
- Department of Child Health CareChildren’s Hospital of Nanjing Medical UniversityNanjingChina
- Institute of Pediatric ResearchNanjing Medical UniversityNanjingChina
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27
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Elsayed HRH, El-Nablaway M, Khattab BA, Sherif RN, Elkashef WF, Abdalla AM, El Nashar EM, Abd-Elmonem MM, El-Gamal R. Independent of Calorie Intake, Short-term Alternate-day Fasting Alleviates NASH, With Modulation of Markers of Lipogenesis, Autophagy, Apoptosis, and Inflammation in Rats. J Histochem Cytochem 2021; 69:575-596. [PMID: 34448436 PMCID: PMC8427931 DOI: 10.1369/00221554211041607] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 07/28/2021] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic steatohepatitis (NASH) is a worldwide health problem. Alternate-day fasting (ADF), although thought to be aggressive, has proven safety and efficacy. We aimed to evaluate the effect of short-term ADF against already established high-fat-fructose (HFF)-induced NASH, independent of the amount of calorie intake, and to study the effect of ADF on lipogenesis, apoptosis, and hepatic inflammation. Male Sprague Dawley rats were divided into two groups: (1) negative control and (2) NASH group fed on HFF for 9 weeks, and then randomized into two subgroups of either HFF alone or with ADF protocol for 3 weeks. The ADF could improve HFF-related elevation in serum lactate dehydrogenase and could decrease the mRNA expression of lipogenesis genes; acetyl CoA carboxylase, peroxisome proliferator-activated receptor γ, and peroxisome proliferator-activated receptor α; apoptotic genes caspase-3, p53, and inflammatory cyclo-oxygenase 2; and immunohistochemical staining for their proteins in liver with upregulation of LC3 and downregulation of P62 immunoexpression. Moreover, ADF ameliorated HFF-induced steatosis, inflammation, ballooning, and fibrosis through hematoxylin and eosin, Oil Red O, and Sirius Red staining, confirmed by morphometric analysis, without significant weight loss. Significant correlation of morphometric parameters with levels of gene expression was found. These findings suggest ADF to be a safe effective therapeutic agent in the management of NASH.
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Affiliation(s)
| | | | | | - Rania N. Sherif
- Department of Anatomy and Embryology
- Department of Anatomy, Horus University, New Damietta, Egypt
| | - Wagdi Fawzy Elkashef
- Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Asim Mohammed Abdalla
- Department of Anatomy, College of Medicine, King Khalid University, Abha, Saudi Arabia
| | - Eman Mohammad El Nashar
- Department of Anatomy, College of Medicine, King Khalid University, Abha, Saudi Arabia
- Department of Histology and Cell Biology, Faculty of Medicine, Benha University, Benha, Egypt
| | | | - Randa El-Gamal
- Department of Medical Biochemistry
- Department of Pathology and Medical Experimental Research Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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28
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Vvedenskaya O, Rose TD, Knittelfelder O, Palladini A, Wodke JAH, Schuhmann K, Ackerman JM, Wang Y, Has C, Brosch M, Thangapandi VR, Buch S, Züllig T, Hartler J, Köfeler HC, Röcken C, Coskun Ü, Klipp E, von Schoenfels W, Gross J, Schafmayer C, Hampe J, Pauling JK, Shevchenko A. Nonalcoholic fatty liver disease stratification by liver lipidomics. J Lipid Res 2021; 62:100104. [PMID: 34384788 PMCID: PMC8488246 DOI: 10.1016/j.jlr.2021.100104] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 07/20/2021] [Accepted: 07/30/2021] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a common metabolic dysfunction leading to hepatic steatosis. However, NAFLD's global impact on the liver lipidome is poorly understood. Using high-resolution shotgun mass spectrometry, we quantified the molar abundance of 316 species from 22 major lipid classes in liver biopsies of 365 patients, including nonsteatotic patients with normal or excessive weight, patients diagnosed with NAFL (nonalcoholic fatty liver) or NASH (nonalcoholic steatohepatitis), and patients bearing common mutations of NAFLD-related protein factors. We confirmed the progressive accumulation of di- and triacylglycerols and cholesteryl esters in the liver of NAFL and NASH patients, while the bulk composition of glycerophospho- and sphingolipids remained unchanged. Further stratification by biclustering analysis identified sphingomyelin species comprising n24:2 fatty acid moieties as membrane lipid markers of NAFLD. Normalized relative abundance of sphingomyelins SM 43:3;2 and SM 43:1;2 containing n24:2 and n24:0 fatty acid moieties, respectively, showed opposite trends during NAFLD progression and distinguished NAFL and NASH lipidomes from the lipidome of nonsteatotic livers. Together with several glycerophospholipids containing a C22:6 fatty acid moiety, these lipids serve as markers of early and advanced stages of NAFL.
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Affiliation(s)
- Olga Vvedenskaya
- Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
| | - Tim Daniel Rose
- LipiTUM, Chair of Experimental Bioinformatics, TUM School of Life Sciences, Technical University of Munich, Munich, Germany
| | - Oskar Knittelfelder
- Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
| | - Alessandra Palladini
- Paul Langerhans Institute Dresden of the Helmholtz Zentrum Munich at the University Hospital Carl Gustav Carus, Technische Universität (TU) Dresden, Dresden, Germany; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
| | | | - Kai Schuhmann
- Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
| | | | - Yuting Wang
- Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
| | - Canan Has
- Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
| | - Mario Brosch
- Department of Medicine I, University Hospital Dresden, Technische Universität (TU) Dresden, Dresden, Germany; Center for Regenerative Therapies Dresden (CRTD), Technische Universität (TU) Dresden, Dresden, Germany
| | - Veera Raghavan Thangapandi
- Department of Medicine I, University Hospital Dresden, Technische Universität (TU) Dresden, Dresden, Germany; Center for Regenerative Therapies Dresden (CRTD), Technische Universität (TU) Dresden, Dresden, Germany
| | - Stephan Buch
- Department of Medicine I, University Hospital Dresden, Technische Universität (TU) Dresden, Dresden, Germany; Center for Regenerative Therapies Dresden (CRTD), Technische Universität (TU) Dresden, Dresden, Germany
| | - Thomas Züllig
- Core Facility Mass Spectrometry, Medical University of Graz, Graz, Austria
| | - Jürgen Hartler
- Institute of Pharmaceutical Sciences, University of Graz, Graz, Austria; Field of Excellence BioHealth, University of Graz, Graz, Austria
| | - Harald C Köfeler
- Core Facility Mass Spectrometry, Medical University of Graz, Graz, Austria
| | - Christoph Röcken
- Department of Pathology, University Hospital Schleswig Holstein, Kiel, Schleswig-Holstein, Germany
| | - Ünal Coskun
- Paul Langerhans Institute Dresden of the Helmholtz Zentrum Munich at the University Hospital Carl Gustav Carus, Technische Universität (TU) Dresden, Dresden, Germany; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany; Department of Membrane Biochemistry and Lipid Research, University Hospital Carl Gustav Carus of Technische Universität Dresden, Dresden, Germany
| | - Edda Klipp
- Theoretical Biophysics, Humboldt-Universität zu Berlin, Berlin, Germany
| | - Witigo von Schoenfels
- Department of Visceral and Thoracic Surgery, University Hospital Schleswig-Holstein, Kiel Campus, Christian-Albrechts-University Kiel, Kiel, Germany; Christian Albrechts University in Kiel Center of Clinical Anatomy Kiel, Schleswig-Holstein, Germany
| | - Justus Gross
- Department of General, Visceral, Vascular and Transplant Surgery, Rostock University Medical Center, Rostock, Germany
| | - Clemens Schafmayer
- Department of General, Visceral, Vascular and Transplant Surgery, Rostock University Medical Center, Rostock, Germany
| | - Jochen Hampe
- Department of Medicine I, University Hospital Dresden, Technische Universität (TU) Dresden, Dresden, Germany
| | - Josch Konstantin Pauling
- LipiTUM, Chair of Experimental Bioinformatics, TUM School of Life Sciences, Technical University of Munich, Munich, Germany.
| | - Andrej Shevchenko
- Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
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Yang FC, Xu F, Wang TN, Chen GX. Roles of vitamin A in the regulation of fatty acid synthesis. World J Clin Cases 2021; 9:4506-4519. [PMID: 34222419 PMCID: PMC8223857 DOI: 10.12998/wjcc.v9.i18.4506] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Revised: 03/25/2021] [Accepted: 04/21/2021] [Indexed: 02/06/2023] Open
Abstract
Dietary macronutrients and micronutrients play important roles in human health. On the other hand, the excessive energy derived from food is stored in the form of triacylglycerol. A variety of dietary and hormonal factors affect this process through the regulation of the activities and expression levels of those key player enzymes involved in fatty acid biosynthesis such as acetyl-CoA carboxylase, fatty acid synthase, fatty acid elongases, and desaturases. As a micronutrient, vitamin A is essential for the health of humans. Recently, vitamin A has been shown to play a role in the regulation of glucose and lipid metabolism. This review summarizes recent research progresses about the roles of vitamin A in fatty acid synthesis. It focuses on the effects of vitamin A on the activities and expression levels of mRNA and proteins of key enzymes for fatty acid synthesis in vitro and in vivo. It appears that vitamin A status and its signaling pathway regulate the expression levels of enzymes involved in fatty acid synthesis. Future research directions are also discussed.
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Affiliation(s)
- Fu-Chen Yang
- Food College, Jiangsu Food and Pharmaceutical College, Huaian 223003, Jiangsu Province, China
| | - Feng Xu
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Tian-Nan Wang
- Department of Nutrition, The University of Tennessee, Knoxville, TN 37909, United States
| | - Guo-Xun Chen
- Department of Nutrition, The University of Tennessee, Knoxville, TN 37909, United States
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Huang Z, Huang S, Song T, Yin Y, Tan C. Placental Angiogenesis in Mammals: A Review of the Regulatory Effects of Signaling Pathways and Functional Nutrients. Adv Nutr 2021; 12:2415-2434. [PMID: 34167152 PMCID: PMC8634476 DOI: 10.1093/advances/nmab070] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 05/05/2021] [Accepted: 05/11/2021] [Indexed: 12/13/2022] Open
Abstract
Normal placental development and proper angiogenesis are essential for fetal growth during pregnancy. Angiogenesis involves the regulatory action of many angiogenic factors and a series of signal transduction processes inside and outside the cell. The obstruction of placental angiogenesis causes fetal growth restriction and serious pregnancy complications, even leading to fetal loss and pregnancy cessation. In this review, the effects of placental angiogenesis on fetal development are described, and several signaling pathways related to placental angiogenesis and their key regulatory mediators are summarized. These factors, which include vascular endothelial growth factor (VEGF)-VEGF receptor, delta-like ligand 4 (DLL-4)-Notch, Wnt, and Hedgehog, may affect the placental angiogenesis process. Moreover, the degree of vascularization depends on cell proliferation, migration, and differentiation, which is affected by the synthesis and secretion of metabolites or intermediates and mutual coordination or inhibition in these pathways. Furthermore, we discuss recent advances regarding the role of functional nutrients (including amino acids and fatty acids) in regulating placental angiogenesis. Understanding the specific mechanism of placental angiogenesis and its influence on fetal development may facilitate the establishment of new therapeutic strategies for the treatment of preterm birth, pre-eclampsia, or intrauterine growth restriction, and provide a theoretical basis for formulating nutritional regulation strategies during pregnancy.
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Affiliation(s)
- Zihao Huang
- Guangdong Laboratory of Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, and National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Shuangbo Huang
- Guangdong Laboratory of Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, and National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Tongxing Song
- Huazhong Agricultural University, College of Animal Science and Technology, Wuhan, China
| | - Yulong Yin
- National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, China
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Lawrence GD. Perspective: The Saturated Fat-Unsaturated Oil Dilemma: Relations of Dietary Fatty Acids and Serum Cholesterol, Atherosclerosis, Inflammation, Cancer, and All-Cause Mortality. Adv Nutr 2021; 12:647-656. [PMID: 33693484 PMCID: PMC8166560 DOI: 10.1093/advances/nmab013] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 11/23/2020] [Accepted: 01/21/2021] [Indexed: 12/27/2022] Open
Abstract
PUFAs are known to regulate cholesterol synthesis and cellular uptake by multiple mechanisms that do not involve SFAs. Polymorphisms in any of the numerous proteins involved in cholesterol homeostasis, as a result of genetic variation, could lead to higher or lower serum cholesterol. PUFAs are susceptible to lipid peroxidation, which can lead to oxidative stress, inflammation, atherosclerosis, cancer, and disorders associated with inflammation, such as insulin resistance, arthritis, and numerous inflammatory syndromes. Eicosanoids from arachidonic acid are among the most powerful mediators that initiate an immune response, and a wide range of PUFA metabolites regulate numerous physiological processes. There is a misconception that dietary SFAs can cause inflammation, although endogenous palmitic acid is converted to ceramides and other cell constituents involved in an inflammatory response after it is initiated by lipid mediators derived from PUFAs. This article will discuss the many misconceptions regarding how dietary lipids regulate serum cholesterol, the fact that all-cause death rate is higher in humans with low compared with normal or moderately elevated serum total cholesterol, the numerous adverse effects of increasing dietary PUFAs or carbohydrate relative to SFAs, as well as metabolic conversion of PUFAs to SFAs and MUFAs as a protective mechanism. Consequently, dietary saturated fats seem to be less harmful than the proposed alternatives.
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Affiliation(s)
- Glen D Lawrence
- Department of Chemistry and Biochemistry, Long Island University, Brooklyn, NY, USA
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Guschina IA, Ninkina N, Roman A, Pokrovskiy MV, Buchman VL. Triple-Knockout, Synuclein-Free Mice Display Compromised Lipid Pattern. Molecules 2021; 26:3078. [PMID: 34064018 PMCID: PMC8196748 DOI: 10.3390/molecules26113078] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 05/05/2021] [Accepted: 05/11/2021] [Indexed: 11/29/2022] Open
Abstract
Recent studies have implicated synucleins in several reactions during the biosynthesis of lipids and fatty acids in addition to their recognised role in membrane lipid binding and synaptic functions. These are among aspects of decreased synuclein functions that are still poorly acknowledged especially in regard to pathogenesis in Parkinson's disease. Here, we aimed to add to existing knowledge of synuclein deficiency (i.e., the lack of all three family members), with respect to changes in fatty acids and lipids in plasma, liver, and two brain regions in triple synuclein-knockout (TKO) mice. We describe changes of long-chain polyunsaturated fatty acids (LCPUFA) and palmitic acid in liver and plasma, reduced triacylglycerol (TAG) accumulation in liver and non-esterified fatty acids in plasma of synuclein free mice. In midbrain, we observed counterbalanced changes in the relative concentrations of phosphatidylcholine (PC) and cerebrosides (CER). We also recorded a notable reduction in ethanolamine plasmalogens in the midbrain of synuclein free mice, which is an important finding since the abnormal ether lipid metabolism usually associated with neurological disorders. In summary, our data demonstrates that synuclein deficiency results in alterations of the PUFA synthesis, storage lipid accumulation in the liver, and the reduction of plasmalogens and CER, those polar lipids which are principal compounds of lipid rafts in many tissues. An ablation of all three synuclein family members causes more profound changes in lipid metabolism than changes previously shown to be associated with γ-synuclein deficiency alone. Possible mechanisms by which synuclein deficiency may govern the reported modifications of lipid metabolism in TKO mice are proposed and discussed.
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Affiliation(s)
- Irina A. Guschina
- School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK; (N.N.); (A.R.); (V.L.B.)
| | - Natalia Ninkina
- School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK; (N.N.); (A.R.); (V.L.B.)
- Institute of Physiologically Active Compounds Russian Academy of Sciences (IPAC RAS), 1 Severniy Proezd, Chernogolovka 142432, Moscow Region, Russia
| | - Andrei Roman
- School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK; (N.N.); (A.R.); (V.L.B.)
- Institute of Physiologically Active Compounds Russian Academy of Sciences (IPAC RAS), 1 Severniy Proezd, Chernogolovka 142432, Moscow Region, Russia
| | - Mikhail V. Pokrovskiy
- Research Institute of Living Systems Pharmacology, Belgorod State National Research University, 85 Pobedy Street, Belgorod 308015, Belgorod Oblast, Russia;
| | - Vladimir L. Buchman
- School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK; (N.N.); (A.R.); (V.L.B.)
- Institute of Physiologically Active Compounds Russian Academy of Sciences (IPAC RAS), 1 Severniy Proezd, Chernogolovka 142432, Moscow Region, Russia
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Eicosapentaenoic acid supplemented to in vitro maturation medium results in lesser lipid content and intracellular reactive oxygen species in blastocysts of cattle. Anim Reprod Sci 2021; 229:106765. [PMID: 33989912 DOI: 10.1016/j.anireprosci.2021.106765] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 05/04/2021] [Accepted: 05/05/2021] [Indexed: 11/20/2022]
Abstract
Sub-optimal cattle embryo development to the blastocyst stage still is a problem when conducting in vitro production (IVP) procedures. Supplementation of in vitro maturation (IVM) medium with omega 3-polyunsaturated eicosapentaenoic acid (EPA) is an approach that might have positive effects on lipid metabolism of cattle oocytes, potentially improving subsequent embryo development. The aim of this study was to evaluate effects of EPA addition to serum-free IVM medium on pronuclear formation after in vitro fertilization, cleavage, and blastocyst rates. Effects of EPA on lipid accumulation and intracellular reactive oxygen species (ROS) generation with IVP of cattle embryos was also investigated. In all experiments, cumulus-oocyte complexes were matured in IVM medium supplemented with 0 nM, 1 nM, or 1 μM EPA for 24 h. Pronuclear formation, cleavage, and blastocyst rates were similar for embryos when there was supplementation of EPA at all concentrations to those of the control group (P > 0.05). The inclusion of 1 nM EPA in medium resulted in a greater lipid content and less intracellular ROS in day 8-embryos compared with those of the Control group (P < 0.05). There were no differences, however, when there was inclusion of 1 μM EPA compared to embryos of the Control group at the day 8 developmental stage (P > 0.05). In conclusion, supplementation with IVM medium with the 1 nM EPA concentration resulted in a lesser blastocyst lipid and intracellular ROS concentration, without modifying embryo development, therefore, EPA could be a desirable supplement to improve embryo quality in cattle.
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Morshedzadeh N, Rahimlou M, Shahrokh S, Karimi S, Mirmiran P, Zali MR. The effects of flaxseed supplementation on metabolic syndrome parameters, insulin resistance and inflammation in ulcerative colitis patients: An open-labeled randomized controlled trial. Phytother Res 2021; 35:3781-3791. [PMID: 33856729 DOI: 10.1002/ptr.7081] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 02/23/2021] [Accepted: 02/25/2021] [Indexed: 12/11/2022]
Abstract
The present study aimed to evaluate the efficacy of flaxseed supplementation in the management of metabolic syndrome (MetS)-related parameters among the patients with mild-to-moderate ulcerative colitis (UC). A randomized controlled clinical trial was conducted on 70 patients with UC. Participants were randomized in the intervention group, which received 30 g/day ground flaxseed powder or control group. Anthropometric and biochemical variables were assessed at the beginning and end of 12 weeks of intervention. Of the 70 patients enrolled in this study, 64 subjects were included in the final analysis. From baseline to 12 weeks' intervention, flaxseed supplementation resulted in a significant reduction in the serum concentration of insulin (p < .001), HOMA-IR (p < .001), triglyceride (p = .001), total cholesterol (p < .001), and significant increase in the serum levels of HDL (p = .008). Also, we found a significant improvement in the SCCAI score (p < .001), TNF-α (p = .03), and CRP (p < .001) following the flaxseed supplementation. However, we not observed any significant differences between two groups regarding the body weight, BMI, waist circumferences, systolic, and diastolic blood pressure (p > .05). Overall, 12 weeks of flaxseed supplementation resulted in greater improvement in the some MetS-related parameters.
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Affiliation(s)
- Nava Morshedzadeh
- Department of Nutrition, Faculty of Public Health, Kerman University of Medical Sciences, Kerman, Iran
| | - Mehran Rahimlou
- Department of Nutrition, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Shabnam Shahrokh
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Soheila Karimi
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Parvin Mirmiran
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Sundrani DP, Karkhanis AR, Joshi SR. Peroxisome Proliferator-Activated Receptors (PPAR), fatty acids and microRNAs: Implications in women delivering low birth weight babies. Syst Biol Reprod Med 2021; 67:24-41. [PMID: 33719831 DOI: 10.1080/19396368.2020.1858994] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Low birth weight (LBW) babies are associated with neonatal morbidity and mortality and are at increased risk for noncommunicable diseases (NCDs) in later life. However, the molecular determinants of LBW are not well understood. Placental insufficiency/dysfunction is the most frequent etiology for fetal growth restriction resulting in LBW and placental epigenetic processes are suggested to be important regulators of pregnancy outcome. Early life exposures like altered maternal nutrition may have long-lasting effects on the health of the offspring via epigenetic mechanisms like DNA methylation and microRNA (miRNA) regulation. miRNAs have been recognized as major regulators of gene expression and are known to play an important role in placental development. Angiogenesis in the placenta is known to be regulated by transcription factor peroxisome proliferator-activated receptor (PPAR) which is activated by ligands such as long-chain-polyunsaturated fatty acids (LCPUFA). In vitro studies in different cell types indicate that fatty acids can influence epigenetic mechanisms like miRNA regulation. We hypothesize that maternal fatty acid status may influence the miRNA regulation of PPAR genes in the placenta in women delivering LBW babies. This review provides an overview of miRNAs and their regulation of PPAR gene in the placenta of women delivering LBW babies.Abbreviations: AA - Arachidonic Acid; Ago2 - Argonaute2; ALA - Alpha-Linolenic Acid; ANGPTL4 - Angiopoietin-Like Protein 4; C14MC - Chromosome 14 miRNA Cluster; C19MC - Chromosome 19 miRNA Cluster; CLA - Conjugated Linoleic Acid; CSE - Cystathionine γ-Lyase; DHA - Docosahexaenoic Acid; EFA - Essential Fatty Acids; E2F3 - E2F transcription factor 3; EPA - Eicosapentaenoic Acid; FGFR1 - Fibroblast Growth Factor Receptor 1; GDM - Gestational Diabetes Mellitus; hADMSCs - Human Adipose Tissue-Derived Mesenchymal Stem Cells; hBMSCs - Human Bone Marrow Mesenchymal Stem Cells; HBV - Hepatitis B Virus; HCC - Hepatocellular Carcinoma; HCPT - Hydroxycamptothecin; HFD - High-Fat Diet; Hmads - Human Multipotent Adipose-Derived Stem; HSCS - Human Hepatic Stellate Cells; IUGR - Intrauterine Growth Restriction; LA - Linoleic Acid; LBW - Low Birth Weight; LCPUFA - Long-Chain Polyunsaturated Fatty Acids; MEK1 - Mitogen-Activated Protein Kinase 1; MiRNA - MicroRNA; mTOR - Mammalian Target of Rapamycin; NCDs - NonCommunicable Diseases; OA - Oleic Acid; PASMC - Pulmonary Artery Smooth Muscle Cell; PLAG1 - Pleiomorphic Adenoma Gene 1; PPAR - Peroxisome Proliferator-Activated Receptor; PPARα - PPAR alpha; PPARγ - PPAR gamma; PPARδ - PPAR delta; pre-miRNA - precursor miRNA; RISC - RNA-Induced Silencing Complex; ROS - Reactive Oxygen Species; SAT - Subcutaneous Adipose Tissue; WHO - World Health Organization.
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Affiliation(s)
- Deepali P Sundrani
- Mother and Child Health, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Pune, India
| | - Aishwarya R Karkhanis
- Mother and Child Health, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Pune, India
| | - Sadhana R Joshi
- Mother and Child Health, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Pune, India
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Uken KL, Schäff CT, Vogel L, Gnott M, Dannenberger D, Görs S, Tuchscherer A, Tröscher A, Liermann W, Hammon HM. Modulation of colostrum composition and fatty acid status in neonatal calves by maternal supplementation with essential fatty acids and conjugated linoleic acid starting in late lactation. J Dairy Sci 2021; 104:4950-4969. [PMID: 33589265 DOI: 10.3168/jds.2020-19627] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Accepted: 11/11/2020] [Indexed: 01/11/2023]
Abstract
Sufficient maternal supply of essential fatty acids (EFA) to neonatal calves is critical for calf development. In the modern dairy cow, EFA supply has shifted from α-linolenic acid (ALA) to linoleic acid (LA) due to the replacement of pasture feeding by corn silage-based diets. As a consequence of reduced pasture feeding, conjugated linoleic acid (CLA) provision by rumen biohydrogenation was also reduced. The present study investigated the fatty acid (FA) status and performance of neonatal calves descended from dams receiving corn silage-based diets and random supplementation of either 76 g/d coconut oil (CTRL; n = 9), 78 g/d linseed oil and 4 g/d safflower oil (EFA; n-6/n-3 FA ratio = 1:3; n = 9), 38 g/d Lutalin (BASF SE, Ludwigshafen, Germany) providing 27% cis-9,trans-11 and trans-10,cis-12 CLA, respectively (CLA; n = 9), or a combination of EFA and CLA (EFA+CLA; n = 11) in the last 9 wk before parturition and following lactation. The experimental period comprised the first 5 d of life, during which calves received colostrum and transition milk from their own dam. The nutrient compositions of colostrum and transition milk were analyzed. Plasma samples were taken after birth and before first colostrum intake and on d 5 of life for FA analyses of the total plasma fat and lipid fractions. Maternal EFA and CLA supplementation partly affected colostrum and transition milk composition but did not change the body weights of calves. Most EFA in calves were found in the phospholipid (PL) and cholesterol ester (CE) fractions of the plasma fat. Maternal EFA supplementation increased the percentage of ALA in all lipid fractions of EFA and EFA+CLA compared with CTRL and CLA calves on d 1 and 5, and the increase was much greater on d 5 than on d 1. The LA concentration increased from d 1 to 5 in the plasma fat and lipid fractions of all groups. The concentrations of docosapentaenoic acid, docosahexaenoic acid, and arachidonic acid in plasma fat were higher on d 1 than on d 5, and the percentage of n-3 metabolites was mainly increased in PL if dams received EFA. The percentage of cis-9,trans-11 CLA was higher in the plasma fat of EFA+CLA than CTRL calves after birth. By d 5, the percentages of both CLA isomers increased, leading to higher proportions in plasma fat of CLA and EFA+CLA than in CTRL and EFA calves. Elevated cis-9,trans-11 CLA enrichment was observed on d 5 in PL, CE, and triglycerides of CLA-treated calves, whereas trans-10,cis-12 CLA could not be detected in individual plasma fractions. These results suggest that an altered maternal EFA and CLA supply can reach the calf via the placenta and particularly via the intake of colostrum and transition milk, whereas the n-3 and n-6 FA metabolites partly indicated a greater transfer via the placenta. Furthermore, the nutrient supply via colostrum and transition milk might be partly modulated by an altered maternal EFA and CLA supply but without consequences on calf performance during the first 5 d of life.
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Affiliation(s)
- K L Uken
- Institute of Nutritional Physiology "Oskar Kellner," Leibniz Institute for Farm Animal Biology (FBN), 18196 Dummerstorf, Germany
| | - C T Schäff
- Institute of Nutritional Physiology "Oskar Kellner," Leibniz Institute for Farm Animal Biology (FBN), 18196 Dummerstorf, Germany
| | - L Vogel
- Institute of Nutritional Physiology "Oskar Kellner," Leibniz Institute for Farm Animal Biology (FBN), 18196 Dummerstorf, Germany
| | - M Gnott
- Institute of Nutritional Physiology "Oskar Kellner," Leibniz Institute for Farm Animal Biology (FBN), 18196 Dummerstorf, Germany
| | - D Dannenberger
- Institute of Muscle Biology and Growth, Leibniz Institute for Farm Animal Biology (FBN), 18196 Dummerstorf, Germany
| | - S Görs
- Institute of Nutritional Physiology "Oskar Kellner," Leibniz Institute for Farm Animal Biology (FBN), 18196 Dummerstorf, Germany
| | - A Tuchscherer
- Institute of Genetics and Biometry, Leibniz Institute for Farm Animal Biology (FBN), 18196 Dummerstorf, Germany
| | | | - W Liermann
- Institute of Nutritional Physiology "Oskar Kellner," Leibniz Institute for Farm Animal Biology (FBN), 18196 Dummerstorf, Germany
| | - H M Hammon
- Institute of Nutritional Physiology "Oskar Kellner," Leibniz Institute for Farm Animal Biology (FBN), 18196 Dummerstorf, Germany.
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Morales-Martínez A, Zamorano-Carrillo A, Montes S, El-Hafidi M, Sánchez-Mendoza A, Soria-Castro E, Martínez-Lazcano JC, Martínez-Gopar PE, Ríos C, Pérez-Severiano F. Rich fatty acids diet of fish and olive oils modifies membrane properties in striatal rat synaptosomes. Nutr Neurosci 2021; 24:1-12. [PMID: 30822260 DOI: 10.1080/1028415x.2019.1584692] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Background: Essential fatty acids (EFAs) and non-essential fatty acids (nEFAs) exert experimental and clinical neuroprotection in neurodegenerative diseases. The main EFAs, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), nEFAs, and oleic acid (OA) contained in olive and fish oils are inserted into the cell membranes, but the exact mechanism through which they exert neuroprotection is still unknown. Objectives and Methods: In this study, we assessed the fatty acids content and membrane fluidity in striatal rat synaptosomes after fatty acid-rich diets (olive- or a fish-oil diet, 15% w/w). Then, we evaluated the effect of enriching striatum synaptosomes with fatty acids on the oxidative damage produced by the prooxidants ferrous sulfate (FeSO4) or quinolinic acid (QUIN). Results and Discussion: Lipid profile analysis in striatal synaptosomes showed that EPA content increased in the fish oil group in comparison with control and olive groups. Furthermore, we found that synaptosomes enriched with fatty acids and incubated with QUIN or FeSO4 showed a significant oxidative damage reduction. Results suggest that EFAs, particularly EPA, improve membrane fluidity and confer antioxidant effect.
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Affiliation(s)
- Adriana Morales-Martínez
- Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía, Ciudad de México, México
- Laboratorio de Investigación de Bioquímica y Biofísica Computacional, ENMH, Instituto Politécnico Nacional, Ciudad de México, México
| | - Absalom Zamorano-Carrillo
- Laboratorio de Investigación de Bioquímica y Biofísica Computacional, ENMH, Instituto Politécnico Nacional, Ciudad de México, México
| | - Sergio Montes
- Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía, Ciudad de México, México
| | - Mohammed El-Hafidi
- Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de México, México
| | - Alicia Sánchez-Mendoza
- Departamento de Farmacología, Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de México, México
| | - Elizabeth Soria-Castro
- Departamento de Patología, Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de México, México
| | | | | | - Camilo Ríos
- Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía, Ciudad de México, México
| | - Francisca Pérez-Severiano
- Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía, Ciudad de México, México
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Abstract
OBJECTIVES The current study examines the placental and maternal lipid profile and expression of genes involved in placental lipid metabolism in women with preeclampsia. METHODS The current study includes normotensive control women (n = 40) and women with preeclampsia (n = 39). Preeclampsia women were further classified into women delivering at term preeclampsia (T-PE; n = 15) and preterm preeclampsia (PT-PE; n = 24). RESULTS There were no significant differences in maternal lipid profile between the T-PE and normotensive control groups. Maternal plasma VLDL (P < 0.05) and ratios of total cholesterol : HDL (P < 0.05), atherogenic index [log (triglycerides/HDL)] (P < 0.01) and apolipoprotein B : apolipoprotein A (P < 0.05) were higher in the PT-PE group as compared with the normotensive control group. Placental total cholesterol and HDL levels were higher (P < 0.05) in the T-PE as compared with the normotensive control group. Higher placental triglycerides (P < 0.05) were observed in PT-PE group compared with T-PE group. Placental mRNA levels of peroxisome proliferator activated receptor α, carnitine palmitoyl transferase-1, cluster of differentiation 36 and lipoprotein lipases were lower (P < 0.05) in the PT-PE than normotensive control group. A negative association of mRNA levels of peroxisome proliferator activated receptor α (r = -0.246, P = 0.032; r = -0.308, P = 0.007, respectively), carnitine palmitoyl transferase-1 (r = -0.292, P = 0.011; r = -0.366, P = 0.001), lipoprotein lipases (r = -0.296, P = 0.010; r = -0.254, P = 0.028) with SBP and DBP was observed. There was a positive association of placental triglycerides (r = 0.244, P = 0.031) with DBP. CONCLUSION Women with preeclampsia exhibit higher lipid : lipoprotein ratios suggesting an atherogenic state particularly in women delivering preterm. Lower expression of genes involved in placental fatty acid oxidation and transport was also observed in preeclampsia.
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Affiliation(s)
- Amrita A Khaire
- Mother and Child Health, Interactive Research School for Health Affairs, Bharati Vidyapeeth (Deemed to be University)
| | - Shivani R Thakar
- Mother and Child Health, Interactive Research School for Health Affairs, Bharati Vidyapeeth (Deemed to be University)
| | - Girija N Wagh
- Department of Obstetrics and Gynecology, Bharati Medical College and Hospital, Bharati Vidyapeeth University, Pune, India
| | - Sadhana R Joshi
- Mother and Child Health, Interactive Research School for Health Affairs, Bharati Vidyapeeth (Deemed to be University)
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Yari Z, Cheraghpour M, Alavian SM, Hedayati M, Eini-Zinab H, Hekmatdoost A. The efficacy of flaxseed and hesperidin on non-alcoholic fatty liver disease: an open-labeled randomized controlled trial. Eur J Clin Nutr 2021; 75:99-111. [PMID: 32647367 DOI: 10.1038/s41430-020-0679-3] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Revised: 05/31/2020] [Accepted: 06/29/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND/OBJECTIVES Non-alcoholic fatty liver disease (NAFLD) is growing in prevalence globally and no definitive evidence for any approved pharmacological approaches for patients with NAFLD has been found yet. This study was aimed to assess the clinical effects of flaxseed and hesperidin in patients with NAFLD. SUBJECTS/METHODS In this randomized, controlled, clinical trial, one hundred eligible patients with NAFLD were enrolled and randomly assigned to four dietary intervention groups including lifestyle modification program (control), lifestyle modification program with 30 g whole flaxseed powder, lifestyle modification program with 1 g hesperidin supplementation, and lifestyle modification program with combination of 30 g flaxseed and 1 g hesperidin (flax-hes) for 12 weeks. The changes in anthropometric parameters, metabolic profiles of glucose and lipids, inflammatory biomarkers and hepatic steatosis and fibrosis were evaluated. RESULTS After the 12-week dietary interventions, significant reductions in body mass index, glucose hemostasis parameters and hepatic steatosis were observed in all groups. Repeated measures analysis of variance revealed a significant effect for time relative to almost all paraclinical parameters. Post hoc analysis with Bonferroni correction revealed that the three intervention groups experienced significant decreases in plasma levels of alanine aminotransferase, indices of insulin resistance and insulin sensitivity, fasting glucose and fatty liver index compared to control (p < 0.008). CONCLUSIONS In conclusion, our study confirmed that hesperidin and flaxseed supplementation improved glucose and lipid metabolism, while reduced inflammation and hepatic steatosis (controlled attenuation parameter) in NAFLD patients. The synergistic effects of their combination were observed on plasma glucose concentration and HOMA-IR.
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Affiliation(s)
- Zahra Yari
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Makan Cheraghpour
- Cancer Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | | | - Mehdi Hedayati
- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hassan Eini-Zinab
- Department of Community Nutrition, National Nutrition and Food Technology Research Institute; and Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Azita Hekmatdoost
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Iwayam K, Ogawa A, Tanaka Y, Yajima K, Park I, Ando A, Ogata H, Kayaba M, Zhang S, Tanji F, Nabekura Y, Yamamoto K, Tokuyama K. Effects of exercise before breakfast on plasma free fatty acid profile and 24-h fat oxidation. Metabol Open 2020; 8:100067. [PMID: 33294835 PMCID: PMC7695873 DOI: 10.1016/j.metop.2020.100067] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Revised: 10/25/2020] [Accepted: 11/12/2020] [Indexed: 11/29/2022] Open
Abstract
Background Free fatty acids (FFAs) are an important source of energy, and also serve as signaling molecules to regulate gene expression. Exercise performed in a post-absorptive state, in contrast to that performed in a postprandial state, increases 24-h fat oxidation under an energy-balanced condition. The primary aim of the present study was to clarify whether the effects of exercise on the concentration and composition of plasma FFAs, which may underlie distinct effects of exercise on 24-h fat oxidation, depend on the nutritional state of the individual when performing the exercise. Methods Ten healthy young men underwent 3 trials of indirect calorimetry in a metabolic chamber. The subjects performed exercise at 60% of VO2max for 60 min in either a post-absorptive or postprandial state, or remained sedentary without an exercise session (control). All trials were designed to be energy balanced over 24 h. Blood samples were collected immediately before and after exercise. Results Fat oxidation over 24 h was increased only when exercise was performed in a post-absorptive state (control, 531 ± 60; post-absorptive, 779 ± 70; postprandial, 569 ± 37 kcal/24 h). The increase in the 24-h fat oxidation was related to the magnitude of the transient carbohydrate deficit after exercise. The plasma FFA concentration after exercise was higher in the post-absorptive trial (0.38 ± 0.04) than in the control (0.13 ± 0.01) and postprandial (0.15 ± 0.02 mM) trials. The ratio of unsaturated to saturated (U/S) fatty acids after exercise was higher in the post-absorptive trial (1.76 ± 0.06) than in the control (1.56 ± 0.07) and postprandial (1.53 ± 0.08) trials. On the other hand, the plasma FFA concentration after exercise in a postprandial state did not differ significantly from that in the control trial. Conclusion Exercise performed in a post-absorptive state effectively increased the plasma FFA concentration and U/S ratio to a greater degree than exercise performed in a postprandial state, underlying the increase in the 24-h fat oxidation. The increase in the plasma FFA concentration was related to the transient carbohydrate deficit after exercise.
Exercise performed in post-absorptive state increases 24-h fat oxidation. Exercise performed in a post-absorptive state increased the ratio of U/S ratio. The plasma FFA concentration was related to the transient carbohydrate deficit.
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Affiliation(s)
- Kaito Iwayam
- Faculty of Budo and Sport Studies, Tenri University, Nara, Japan
| | - Ayane Ogawa
- Program in Sports Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan
- AIM SERVICES CO., LTD, Tokyo, Japan
| | - Yoshiaki Tanaka
- Program in Sports Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan
| | - Katsuhiko Yajima
- Department of Nutritional Physiology, Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan
| | - Insung Park
- International Institute for Integrative Sleep Medicine, University of Tsukuba, Ibaraki, Japan
| | - Akira Ando
- Program in Sports Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan
| | - Hitomi Ogata
- Graduate School of Integrated Arts and Sciences, Hiroshima University, Hiroshima, Japan
| | - Momoko Kayaba
- Department of Somnology, Tokyo Medical University, Tokyo, Japan
| | - Simeng Zhang
- International Institute for Integrative Sleep Medicine, University of Tsukuba, Ibaraki, Japan
| | - Fumiya Tanji
- Sport Medical Science Research Institute, Tokai University, Kanagawa, Japan
| | - Yoshiharu Nabekura
- Program in Sports Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan
| | - Kouhei Yamamoto
- School of Comprehensive Rehabilitation, Osaka Prefecture University, Osaka, Japan
| | - Kumpei Tokuyama
- International Institute for Integrative Sleep Medicine, University of Tsukuba, Ibaraki, Japan
- Corresponding author.
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Sasson A, Kristoferson E, Batista R, McClung JA, Abraham NG, Peterson SJ. The pivotal role of heme Oxygenase-1 in reversing the pathophysiology and systemic complications of NAFLD. Arch Biochem Biophys 2020; 697:108679. [PMID: 33248947 DOI: 10.1016/j.abb.2020.108679] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 11/03/2020] [Accepted: 11/12/2020] [Indexed: 02/06/2023]
Abstract
The pathogenesis and molecular pathways involved in non-alcoholic fatty liver disease (NAFLD) are reviewed, as well as what is known about mitochondrial dysfunction that leads to heart disease and the progression to steatohepatitis and hepatic fibrosis. We focused our discussion on the role of the antioxidant gene heme oxygenase-1 (HO-1) and its nuclear coactivator, peroxisome proliferator-activated receptor-gamma coactivator (PGC1-α) in the regulation of mitochondrial biogenesis and function and potential therapeutic benefit for cardiac disease, NAFLD as well as the pharmacological effect they have on the chronic inflammatory state of obesity. The result is increased mitochondrial function and the conversion of white adipocyte tissue to beige adipose tissue ("browning of white adipose tissue") that leads to an improvement in signaling pathways and overall liver function. Improved mitochondrial biogenesis and function is essential to preventing the progression of hepatic steatosis to NASH and cirrhosis as well as preventing cardiovascular complications.
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Affiliation(s)
- Ariel Sasson
- Department of Medicine, New York Medical College, Valhalla, NY, 10595, USA; Department of Pharmacology, New York Medical College, Valhalla, NY, 10595, USA
| | - Eva Kristoferson
- Department of Medicine, New York Medical College, Valhalla, NY, 10595, USA
| | - Rogerio Batista
- The Mount Sinai Bone Program, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
| | - John A McClung
- Department of Medicine, New York Medical College, Valhalla, NY, 10595, USA
| | - Nader G Abraham
- Department of Medicine, New York Medical College, Valhalla, NY, 10595, USA; Department of Pharmacology, New York Medical College, Valhalla, NY, 10595, USA; Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, 25701, USA
| | - Stephen J Peterson
- Department of Medicine, Weill Cornell Medicine, New York, NY, 10065, USA; New York Presbyterian Brooklyn Methodist Hospital, Brooklyn, NY, 11215, USA.
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Effect of supplementing palmitic acid and altering the dietary ratio of n-6: n-3 fatty acids in low-fibre diets on production responses of dairy cows. Br J Nutr 2020; 126:355-365. [PMID: 33081853 DOI: 10.1017/s0007114520004183] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Supplementing palmitic acid (C16 : 0) in combination with modifying the dietary n-6:n-3 fatty acid (FA) ratio may benefit energy metabolism and milk responses of dairy cows. Twelve Holstein cows (70 (sd 11) days in milk) were used in a replicated 4 × 4 Latin square and allocated to four low-fibre diets (18·5 % forage neutral-detergent fibre) supplemented with no FA (CON), or 2·4 % C16 : 0-enriched supplement (PAL), 2·4 % mixture (2:1) of C16 : 0 and n-6 FA (PW6), and mixture (2:1) of C16 : 0 and n-3 FA (PW3). The dietary ratio of n-6:n-3 was increased with PW6 (10:1) and decreased with PW3 (2·8:1), whereas PAL alone made no change in the ratio (about 7:1). Compared with CON, all FA-supplemented treatments increased milk yield. However, feed and energy intakes were higher in PAL than PW3 or PW6, resulting in greater feed efficiency for PW3 and PW6 than PAL. Dietary FA supplements decreased milk protein concentration but tended to increase protein yield. Compared with CON and FA mixtures, PAL increased milk fat content and tended to increase milk SFA and atherosclerotic index. The concentration of milk n-3 FA was similar between CON and PW3. Feeding PAL increased milk energy output and decreased energy partitioning towards body reserves (-4·2 %), while this measure was positive for other treatments. Blood TAG and NEFA concentrations, but not β-hydroxybutyrate, were increased by FA-supplemented treatments. Feeding C16 : 0 combined with either n-6 or n-3 FA enhanced feed efficiency, alleviated the negative impacts on body energy reserves, but lowering the dietary n-6:n-3 ratio improved the FA profile of milk.
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Acharya P, Uppin V, Zarei M, Talahalli RR. Role of n-3 Fatty Acids on Bile Acid Metabolism and Transport in Dyslipidemia: A Review. Lipids 2020; 56:125-139. [PMID: 33074554 DOI: 10.1002/lipd.12289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Revised: 05/19/2020] [Accepted: 09/22/2020] [Indexed: 11/06/2022]
Abstract
Dietary n-3 fatty acids, especially of marine origin, eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3), have always been lauded for their profound effects on regulating the risk factors for major metabolic disorders. Yet, their consumption rate is poor compared to n-6 fatty acids [linoleic acid (18:2n-6)], which are predominantly consumed. Hence, the skewed n-6 to n-3 fatty acid ratio may have a bearing on the risk factors of various diseases, including dyslipidemia. Dyslipidemia and other lifestyle diseases associated with it, such as diabetes, obesity, hypertension, are a growing concern in both developed and developing countries. A common strategy for addressing dyslipidemia involves bile acid (BA) sequestration, to interrupt the enterohepatic circulation of BA, resulting in the modulation of lipid absorption in the intestine, thereby normalizing the levels of circulating lipids. The BA homeostasis is under the tight control of hepatic and enteric BA transporters. Many investigations have reported the effects of dietary constituents, including certain fatty acids on the reabsorption and transport of BA. However, a critical review of the effects of n-3 fatty acids on BA metabolism and transport is not available. The present review attempts to explore certain unmapped facets of the n-3 fatty acids on BA metabolism and transport in dyslipidemia, and their interplay with biological processes involving lipid rafts and gut microbiome.
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Affiliation(s)
- Pooja Acharya
- Department of Biochemistry, CSIR-Central Food Technological Research Institute, KRS Road, Mysore, Karnataka, 570020, India.,Academy of Scientific and Innovative Research (AcSIR), Kamla Nehru Nagar, Ghaziabad, Uttar Pradesh, 201002, India
| | - Vinayak Uppin
- Department of Biochemistry, CSIR-Central Food Technological Research Institute, KRS Road, Mysore, Karnataka, 570020, India.,Academy of Scientific and Innovative Research (AcSIR), Kamla Nehru Nagar, Ghaziabad, Uttar Pradesh, 201002, India
| | - Mehrdad Zarei
- Department of Biochemistry, CSIR-Central Food Technological Research Institute, KRS Road, Mysore, Karnataka, 570020, India
| | - Ramaprasad R Talahalli
- Department of Biochemistry, CSIR-Central Food Technological Research Institute, KRS Road, Mysore, Karnataka, 570020, India.,Academy of Scientific and Innovative Research (AcSIR), Kamla Nehru Nagar, Ghaziabad, Uttar Pradesh, 201002, India
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Mandala A, Janssen RC, Palle S, Short KR, Friedman JE. Pediatric Non-Alcoholic Fatty Liver Disease: Nutritional Origins and Potential Molecular Mechanisms. Nutrients 2020; 12:E3166. [PMID: 33081177 PMCID: PMC7602751 DOI: 10.3390/nu12103166] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 10/12/2020] [Accepted: 10/13/2020] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the number one chronic liver disease worldwide and is estimated to affect nearly 40% of obese youth and up to 10% of the general pediatric population without any obvious signs or symptoms. Although the early stages of NAFLD are reversible with diet and lifestyle modifications, detecting such stages is hindered by a lack of non-invasive methods of risk assessment and diagnosis. This absence of non-invasive means of diagnosis is directly related to the scarcity of long-term prospective studies of pediatric NAFLD in children and adolescents. In the majority of pediatric NAFLD cases, the mechanisms driving the origin and rapid progression of NAFLD remain unknown. The progression from NAFLD to non-alcoholic steatohepatitis (NASH) in youth is associated with unique histological features and possible immune processes and metabolic pathways that may reflect different mechanisms compared with adults. Recent data suggest that circulating microRNAs (miRNAs) are important new biomarkers underlying pathways of liver injury. Several factors may contribute to pediatric NAFLD development, including high-sugar diets, in utero exposures via epigenetic alterations, changes in the neonatal microbiome, and altered immune system development and mitochondrial function. This review focuses on the unique aspects of pediatric NAFLD and how nutritional exposures impact the immune system, mitochondria, and liver/gastrointestinal metabolic health. These factors highlight the need for answers to how NAFLD develops in children and for early stage-specific interventions.
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Affiliation(s)
- Ashok Mandala
- Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (A.M.); (R.C.J.); (K.R.S.)
| | - Rachel C. Janssen
- Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (A.M.); (R.C.J.); (K.R.S.)
| | - Sirish Palle
- Department of Pediatrics, Section of Gastroenterology, Hepatology & Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA;
| | - Kevin R. Short
- Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (A.M.); (R.C.J.); (K.R.S.)
- Department of Pediatrics, Section of Diabetes and Endocrinology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Jacob E. Friedman
- Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (A.M.); (R.C.J.); (K.R.S.)
- Department of Pediatrics, Section of Diabetes and Endocrinology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
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Boesche K, Donkin S. Pretreatment with saturated and unsaturated fatty acids regulates fatty acid oxidation in Madin-Darby bovine kidney cells. J Dairy Sci 2020; 103:8841-8852. [DOI: 10.3168/jds.2020-18802] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Accepted: 05/29/2020] [Indexed: 01/22/2023]
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Moore MP, Cunningham RP, Dashek RJ, Mucinski JM, Rector RS. A Fad too Far? Dietary Strategies for the Prevention and Treatment of NAFLD. Obesity (Silver Spring) 2020; 28:1843-1852. [PMID: 32893456 PMCID: PMC7511422 DOI: 10.1002/oby.22964] [Citation(s) in RCA: 61] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Revised: 06/04/2020] [Accepted: 06/06/2020] [Indexed: 12/13/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a major health problem, and its prevalence has increased in recent years, concurrent with rising rates of obesity and other metabolic diseases. Currently, there are no FDA-approved pharmacological therapies for NAFLD, and lifestyle interventions, including weight loss and exercise, remain the cornerstones for treatment. Manipulating diet composition and eating patterns may be a sustainable approach to NAFLD treatment. Dietary strategies including Paleolithic, ketogenic, Mediterranean, high-protein, plant-based, low-carbohydrate, and intermittent fasting diets have become increasingly popular because of their purported benefits on metabolic disease. This review highlights what is currently known about these popular dietary approaches in the management of NAFLD in clinical populations with mechanistic insight from animal studies. It also identifies key knowledge gaps to better inform future preclinical and clinical studies aimed at the treatment of NAFLD.
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Affiliation(s)
- Mary P. Moore
- Research Service, Harry S Truman Memorial Veterans Medical Center, Columbia, MO, 65211
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211
| | - Rory P. Cunningham
- Research Service, Harry S Truman Memorial Veterans Medical Center, Columbia, MO, 65211
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211
| | - Ryan J. Dashek
- Research Service, Harry S Truman Memorial Veterans Medical Center, Columbia, MO, 65211
- Comparative Medicine Program, University of Missouri, Columbia, MO 65211
| | - Justine M. Mucinski
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211
| | - R. Scott Rector
- Research Service, Harry S Truman Memorial Veterans Medical Center, Columbia, MO, 65211
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211
- Medicine-Division of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65211
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Effect of High Dietary Level (8%) of Fish Oil on Long-Chain Polyunsaturated Fatty Acid n-3 Content in Pig Tissues and Plasma Biochemical Parameters. Animals (Basel) 2020; 10:ani10091657. [PMID: 32942761 PMCID: PMC7552211 DOI: 10.3390/ani10091657] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 09/11/2020] [Accepted: 09/12/2020] [Indexed: 12/11/2022] Open
Abstract
Simple Summary Fish oil is a source of “healthy” polyunsaturated fatty acids that decrease the risk of cardiovascular and other chronic diseases in humans. One possible way to increase consumption of these fatty acids is to incorporate them into pork via pig-feed. We enriched the pigs’ diet with 8% fish oil and found a several-times higher content of the above-mentioned fatty acids in the pig meat in comparison with controls. The meat of the fish oil-fed pigs was also more tender. We also used the same pigs as a model for testing the effects of the high level of dietary fish oil on selected markers of their state of health and detected an increased level of plasma lipids (risk factor for cardiovascular diseases) and a possible overreaction of the immune system. In conclusion, we can recommend consumption of polyunsaturated fatty acids-enriched “functional” pork, but direct human consumption of fish oil should be limited and in accordance with the recommendation of a moderate intake. Abstract There were two objectives of the present study using dietary fish oil (FO) in pigs: to use pigs as a model for studying the effects of high FO doses on selected physiological markers; and to evaluate the physical traits and nutritive value of pork enriched with long-chain polyunsaturated fatty acids n-3. Two groups of six female pigs were fed for 30 days with either a standard feed mixture (control, C) or the same mixture supplemented with 8% FO (F). Physical characteristics of the muscle, fatty acid deposition in tissues and selected hematologic and plasma markers were tested. The daily weight gain of the F-pigs was lower in comparison with controls (p < 0.05). Dietary fish oil decreased Warner-Bratzler shear force of the longissimus muscle (p < 0.01). The eicosapentaenoic and docosahexaenoic acid content was higher (p < 0.05) in all tested F-tissues. Dietary fish oil had no effect on plasma cholesterol (p < 0.05), but it increased plasma triacylglycerol levels by 260% (p < 0.05), and increased counts of leukocytes, neutrophils, and eosinophils in the blood plasma (p < 0.05). In conclusion, high dietary FO improved the texture and nutritive value of meat, but negatively affected plasma biochemical parameters.
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Hishikawa D, Yanagida K, Nagata K, Kanatani A, Iizuka Y, Hamano F, Yasuda M, Okamura T, Shindou H, Shimizu T. Hepatic Levels of DHA-Containing Phospholipids Instruct SREBP1-Mediated Synthesis and Systemic Delivery of Polyunsaturated Fatty Acids. iScience 2020; 23:101495. [PMID: 32891885 PMCID: PMC7481256 DOI: 10.1016/j.isci.2020.101495] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 07/25/2020] [Accepted: 08/19/2020] [Indexed: 12/25/2022] Open
Abstract
Polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA) and arachidonic acid (ARA), play fundamental roles in mammalian physiology. Although PUFA imbalance causes various disorders, mechanisms of the regulation of their systemic levels are poorly understood. Here, we report that hepatic DHA-containing phospholipids (DHA-PLs) determine the systemic levels of PUFAs through the SREBP1-mediated transcriptional program. We demonstrated that liver-specific deletion of Agpat3 leads to a decrease of DHA-PLs and a compensatory increase of ARA-PLs not only in the liver but also in other tissues including the brain. Together with recent findings that plasma lysophosphatidylcholine (lysoPC) is the major source of brain DHA, our results indicate that hepatic AGPAT3 contributes to brain DHA accumulation by supplying DHA-PLs as precursors of DHA-lysoPC. Furthermore, dietary fish oil-mediated suppression of hepatic PUFA biosynthetic program was blunted in liver-specific Agpat3 deletion. Our findings highlight the central role of hepatic DHA-PLs as the molecular rheostat for systemic homeostasis of PUFAs.
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Affiliation(s)
- Daisuke Hishikawa
- Department of Lipid Signaling, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo 162-8655, Japan.
| | - Keisuke Yanagida
- Department of Lipid Signaling, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo 162-8655, Japan
| | - Katsuyuki Nagata
- Department of Lipid Signaling, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo 162-8655, Japan
| | - Ayumi Kanatani
- Department of Lipid Signaling, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo 162-8655, Japan
| | - Yoshiko Iizuka
- Department of Lipid Signaling, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo 162-8655, Japan
| | - Fumie Hamano
- Department of Lipid Signaling, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo 162-8655, Japan; Life Science Core Faculty, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan
| | - Megumi Yasuda
- Department of Lipid Signaling, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo 162-8655, Japan
| | - Tadashi Okamura
- Laboratory Animal Medicine, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo 162-8655, Japan; Section of Animal Models, Department of Infectious Diseases, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo 162-8655, Japan
| | - Hideo Shindou
- Department of Lipid Signaling, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo 162-8655, Japan; Department of Lipid Science, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan
| | - Takao Shimizu
- Department of Lipid Signaling, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo 162-8655, Japan; Department of Lipidomics, Graduate School of Medicine, the University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
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Bertolini F, Jørgensen MGP, Henkel C, Dufour S, Tomkiewicz J. Unravelling the changes during induced vitellogenesis in female European eel through RNA-Seq: What happens to the liver? PLoS One 2020; 15:e0236438. [PMID: 32790680 PMCID: PMC7425897 DOI: 10.1371/journal.pone.0236438] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Accepted: 07/06/2020] [Indexed: 11/24/2022] Open
Abstract
The life cycle of European eel (Anguilla anguilla), a catadromous species, is complex and enigmatic. In nature, during the silvering process prior to their long spawning migration, reproductive development is arrested, and they cease feeding. In studies of reproduction using hormonal induction, eels are equivalently not feed. Therefore, in female eels that undergo vitellogenesis, the liver plays different, essential roles being involved both in vitellogenins synthesis and in reallocating resources for the maintenance of vital functions, performing the transoceanic reproductive migration and completing reproductive development. The present work aimed at unravelling the major transcriptomic changes that occur in the liver during induced vitellogenesis in female eels. mRNA-Seq data from 16 animals (eight before induced vitellogenesis and eight after nine weeks of hormonal treatment) were generated and differential expression analysis was performed comparing the two groups. This analysis detected 1,328 upregulated and 1,490 downregulated transcripts. Overrepresentation analysis of the upregulated genes included biological processes related to biosynthesis, response to estrogens, mitochondrial activity and localization, while downregulated genes were enriched in processes related to morphogenesis and development of several organs and tissues, including liver and immune system. Among key genes, the upregulated ones included vitellogenin genes (VTG1 and VTG2) that are central in vitellogenesis, together with ESR1 and two novel genes not previously investigated in European eel (LMAN1 and NUPR1), which have been linked with reproduction in other species. Moreover, several upregulated genes, such as CYC1, ELOVL5, KARS and ACSS1, are involved in the management of the effect of fasting and NOTCH, VEGFA and NCOR are linked with development, autophagy and liver maintenance in other species. These results increase the understanding of the molecular changes that occur in the liver during vitellogenesis in this complex and distinctive fish species, bringing new insights on European eel reproduction and broodstock management.
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Affiliation(s)
- Francesca Bertolini
- National Institute of Aquatic Resources, Technical University of Denmark, Lyngby, Denmark
- * E-mail:
| | | | - Christiaan Henkel
- Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Oslo, Norway
| | - Sylvie Dufour
- Laboratory BOREA, Museum National d’Histoire Naturelle, CNRS, Sorbonne University, Paris, France
| | - Jonna Tomkiewicz
- National Institute of Aquatic Resources, Technical University of Denmark, Lyngby, Denmark
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Brandt A, Rajcic D, Jin CJ, Sánchez V, Engstler AJ, Jung F, Nier A, Baumann A, Bergheim I. Fortifying diet with rapeseed oil instead of butterfat attenuates the progression of diet-induced non-alcoholic fatty liver disease (NAFLD) and impairment of glucose tolerance. Metabolism 2020; 109:154283. [PMID: 32497536 DOI: 10.1016/j.metabol.2020.154283] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 05/28/2020] [Accepted: 06/01/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND Absolute dietary fat intake but even more so fatty acid pattern is discussed to be critical in the development of non-alcoholic fatty liver disease (NAFLD). Here, we determined if switching a butterfat enriched diet to a rapeseed oil (RO) enriched diet affects progression of an existing NAFLD and glucose intolerance in mice. METHODS For eight weeks, female C57Bl/6J mice were either fed a liquid control (C) or a butterfat-, fructose- and cholesterol-rich diet (BFC, 25E% butterfat) to induce early signs of steatohepatitis and glucose intolerance in mice. For additional five weeks mice received either BFC or C or a fat-, fructose- and cholesterol-rich and control diet, in which butterfat was replaced with RO (ROFC and CRO). Markers of glucose metabolism, liver damage and intestinal barrier were assessed. RESULTS Exchanging butterfat with RO attenuated the progression of BFC diet-induced NAFLD and glucose intolerance. Beneficial effects of RO were associated with lower portal endotoxin levels and an attenuation of the induction of the toll-like receptor-4-dependent signaling cascades in liver. Peroxisome proliferator-activated receptor γ activity was induced in small intestine of ROFC-fed mice. CONCLUSION Taken together, exchanging butterfat with RO attenuated the progression of diet-induced steatohepatitis and glucose intolerance in mice.
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Affiliation(s)
- Annette Brandt
- Department of Nutritional Sciences, R.F. Molecular Nutritional Science, University of Vienna, Vienna, Austria
| | - Dragana Rajcic
- Department of Nutritional Sciences, R.F. Molecular Nutritional Science, University of Vienna, Vienna, Austria
| | - Cheng Jun Jin
- Institute of Nutrition, SD Model Systems of Molecular Nutrition, Friedrich-Schiller University of Jena, Jena, Germany
| | - Victor Sánchez
- Department of Nutritional Sciences, R.F. Molecular Nutritional Science, University of Vienna, Vienna, Austria
| | - Anna Janina Engstler
- Department of Nutritional Sciences, R.F. Molecular Nutritional Science, University of Vienna, Vienna, Austria
| | - Finn Jung
- Department of Nutritional Sciences, R.F. Molecular Nutritional Science, University of Vienna, Vienna, Austria
| | - Anika Nier
- Department of Nutritional Sciences, R.F. Molecular Nutritional Science, University of Vienna, Vienna, Austria
| | - Anja Baumann
- Department of Nutritional Sciences, R.F. Molecular Nutritional Science, University of Vienna, Vienna, Austria
| | - Ina Bergheim
- Department of Nutritional Sciences, R.F. Molecular Nutritional Science, University of Vienna, Vienna, Austria.
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