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Mignini I, Piccirilli G, Di Vincenzo F, Covello C, Pizzoferrato M, Esposto G, Galasso L, Borriello R, Gabrielli M, Ainora ME, Gasbarrini A, Zocco MA. Intestinal-Failure-Associated Liver Disease: Beyond Parenteral Nutrition. Biomolecules 2025; 15:388. [PMID: 40149924 PMCID: PMC11939910 DOI: 10.3390/biom15030388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2025] [Revised: 03/05/2025] [Accepted: 03/06/2025] [Indexed: 03/29/2025] Open
Abstract
Short bowel syndrome (SBS), usually resulting from massive small bowel resections or congenital defects, may lead to intestinal failure (IF), requiring intravenous fluids and parenteral nutrition to preserve patients' nutritional status. Approximately 15% to 40% of subjects with SBS and IF develop chronic hepatic damage during their life, a condition referred to as intestinal-failure-associated liver disease (IFALD), which ranges from steatosis to fibrosis or end-stage liver disease. Parenteral nutrition has been largely pointed out as the main pathogenetic factor for IFALD. However, other elements, such as inflammation, bile acid metabolism, bacterial overgrowth and gut dysbiosis also contribute to the development of liver damage and may deserve specific treatment strategies. Indeed, in our review, we aim to explore IFALD pathogenesis beyond parenteral nutrition. By critically analyzing recent literature, we seek to delve with molecular mechanisms and metabolic pathways underlying liver damage in such a complex set of patients.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Maria Assunta Zocco
- CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (I.M.); (G.P.); (F.D.V.); (C.C.); (M.P.); (G.E.); (L.G.); (R.B.); (M.G.); (M.E.A.); (A.G.)
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Waś J, Dobrowolski P, Prejbisz A, Niedolistek M, Kowalik I, Drohomirecka A, Sokołowska D, Krzysztoń-Russjan J. Early Changes in the Plasma Lipidome of People at Very High Cardiovascular Risk: A New Approach to Assessing the Risk of Cardiovascular Changes. Biomedicines 2025; 13:643. [PMID: 40149619 PMCID: PMC11940131 DOI: 10.3390/biomedicines13030643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Revised: 02/25/2025] [Accepted: 03/04/2025] [Indexed: 03/29/2025] Open
Abstract
Background/Objectives: Cardiovascular disease (CVD) remains the leading cause of death worldwide and requires a deeper understanding of its pathogenesis for effective prevention and treatment. Familial hypercholesterolemia (FH), characterized by high levels of LDL cholesterol, is a significant risk factor for CVD. FH background remains unexplained despite advances in genetic testing. The aim was identification early changes in the plasma lipidome of individuals at high cardiovascular risk (HCVR) using liquid chromatography coupled with mass spectrometry. Methods: The lipidomic analysis examined over 400 compounds. Twenty individuals with suspected FH, very high cardiovascular risk (VHCVR), and undetectable mutations in the LDLR, APOB, or PCSK9 genes were compared to control group in a qualitative-quantitative analysis. Results: Multivariate analyses revealed statistically significant alterations in glycerophospholipids (GC), with a notable increase in phosphatidylcholines ((O-36:0/16:0), OR (95% CI): 1.246 (1.042-1.490), p = 0.0157), phosphatidylethanolamines ((O-40:7/22:6), OR (95% CI): 1.119 (1.039-1.205), p = 0.0028), and phosphatidylglycerol ((40:8/20:4), OR (95% CI): 1.053 (1.008-1.101), p = 0.0219) only in patients with HCVR. These changes, particularly in major classes of GC, underscored their potential as biomarkers for early assessment of cardiovascular risk. Lipidomic profiling revealed associations between specific lipid species and the comorbidities of arterial hypertension, atherosclerosis, and insulin resistance, implicating their role in atherosclerotic cardiovascular disease (ASCVD). Conclusions: This study points early changes in the plasma lipidome in individuals at HCVR, underline potential biomarkers, therapeutic targets for ASCVD, and offer opportunities to improve ASCVD diagnosis, therapy, and risk management strategies through detailed personalized medical approach.
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Affiliation(s)
- Joanna Waś
- Department of Medical Biology, National Institute of Cardiology, State Research Institute, 42 Alpejska Str., 04-628 Warsaw, Poland; (M.N.); (D.S.); (J.K.-R.)
| | - Piotr Dobrowolski
- Department of Epidemiology, Cardiovascular Disease Prevention and Health Promotion, National Institute of Cardiology, State Research Institute, 42 Alpejska Str., 04-628 Warsaw, Poland; (P.D.); (A.P.)
| | - Aleksander Prejbisz
- Department of Epidemiology, Cardiovascular Disease Prevention and Health Promotion, National Institute of Cardiology, State Research Institute, 42 Alpejska Str., 04-628 Warsaw, Poland; (P.D.); (A.P.)
| | - Magdalena Niedolistek
- Department of Medical Biology, National Institute of Cardiology, State Research Institute, 42 Alpejska Str., 04-628 Warsaw, Poland; (M.N.); (D.S.); (J.K.-R.)
| | - Ilona Kowalik
- Clinical Research Support Centre, National Institute of Cardiology, State Research Institute, 42 Alpejska Str., 04-628 Warsaw, Poland;
| | - Anna Drohomirecka
- Heart Failure and Transplantology Clinic, National Institute of Cardiology, State Research Institute, 42 Alpejska Str., 04-628 Warsaw, Poland;
| | - Dorota Sokołowska
- Department of Medical Biology, National Institute of Cardiology, State Research Institute, 42 Alpejska Str., 04-628 Warsaw, Poland; (M.N.); (D.S.); (J.K.-R.)
| | - Jolanta Krzysztoń-Russjan
- Department of Medical Biology, National Institute of Cardiology, State Research Institute, 42 Alpejska Str., 04-628 Warsaw, Poland; (M.N.); (D.S.); (J.K.-R.)
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Yaqoob MU, Qi Y, Hou J, Zhe L, Zhu X, Wu P, Li Z, Wang M, Li Y, Yue M. Coated cysteamine and choline chloride could be potential feed additives to mitigate the harmful effects of fatty liver hemorrhagic syndrome in laying hens caused by high-energy low-protein diet. Poult Sci 2024; 103:104296. [PMID: 39305615 PMCID: PMC11437759 DOI: 10.1016/j.psj.2024.104296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 08/30/2024] [Accepted: 08/31/2024] [Indexed: 10/01/2024] Open
Abstract
The research aimed to examine the impact of coated cysteamine (CS) and choline chloride (CC) on relieving the pathological effects of fatty liver hemorrhagic syndrome (FLHS) in laying hens. FLHS was induced by a high-energy low-protein (HELP) diet. Ninety laying hens were equally divided into 5 treatments with 6 replicates per treatment (3 hens/replicate). The control treatment (Cont) was fed a basal diet, while the remaining treatments were fed a HELP diet. Under the HELP dietary plan, 4 treatments were set by a 2 × 2 factorial design. Two levels of CS (CS-: 0.00 mg/kg CS; CS+: 100 mg/kg diet) and 2 levels of choline (CC-: 1,182 mg/kg; CC+: 4,124 mg/kg) were set and named CS-CC- (HELP), CS+CC-, CS-CC+ and CS+CC+. The liver of the CS-CC- (HELP) group became yellowish-brown and greasy, with hemorrhages and bleeding spots. Elevated (P < 0.05) plasma and hepatic ALT and AST and hepatic MDA levels, combined with reduced (P < 0.05) plasma and hepatic SOD and GSH-Px activities in the CS-CC- (HELP) group proved that FLHS was successfully induced. Dietary supplementation of CS, CC, or both (CS+CC+) in HELP diets relieved the pathological changes, significantly (P < 0.05) reduced the AST and ALT levels, and strengthened the antioxidant potential in laying hens under FLHS. The highest (P < 0.001) plasma adiponectin concentration was observed in the CS+CC- and lowest in the CS-CC- (HELP) group. In addition, CS and CC supplementation lowers the elevated levels of hepatic T-CHO and TG by increasing the HDL-C and reducing LDL-C levels (P < 0.05) than CS-CC- (HELP) group. CS supplementation, either alone or with CC, helps laying hens restore their egg production. It could be stated that CS and CC supplements could ameliorate the adverse effects of FLHS by regulating antioxidant enzymes activities, modulating the hepatic lipid metabolism, and restoring the production performance in laying hens. Hence, adding CS and CC could be an effective way to reduce FLHS in laying hens.
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Affiliation(s)
- Muhammad Umar Yaqoob
- College of Animal Science, Zhejiang University, Hangzhou 310058, China; Provincial Key Agricultural Enterprise Research Institute of King Techina, Hangzhou King Techina Feed Co., Ltd. Zhejiang Hangzhou 311107, China
| | - Yingying Qi
- Provincial Key Agricultural Enterprise Research Institute of King Techina, Hangzhou King Techina Feed Co., Ltd. Zhejiang Hangzhou 311107, China
| | - Jia Hou
- Provincial Key Agricultural Enterprise Research Institute of King Techina, Hangzhou King Techina Feed Co., Ltd. Zhejiang Hangzhou 311107, China
| | - Li Zhe
- Provincial Key Agricultural Enterprise Research Institute of King Techina, Hangzhou King Techina Feed Co., Ltd. Zhejiang Hangzhou 311107, China
| | - Xiangde Zhu
- Provincial Key Agricultural Enterprise Research Institute of King Techina, Hangzhou King Techina Feed Co., Ltd. Zhejiang Hangzhou 311107, China
| | - Peng Wu
- Provincial Key Agricultural Enterprise Research Institute of King Techina, Hangzhou King Techina Feed Co., Ltd. Zhejiang Hangzhou 311107, China
| | - Zhefeng Li
- Provincial Key Agricultural Enterprise Research Institute of King Techina, Hangzhou King Techina Feed Co., Ltd. Zhejiang Hangzhou 311107, China
| | - Minqi Wang
- College of Animal Science, Zhejiang University, Hangzhou 310058, China
| | - Yan Li
- College of Animal Science, Zhejiang University, Hangzhou 310058, China
| | - Min Yue
- College of Animal Science, Zhejiang University, Hangzhou 310058, China; Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, China.
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Karino S, Usuda H, Kanda S, Okamoto T, Niibayashi T, Yano T, Naora K, Wada K. A diet high in glucose and deficient in dietary fibre causes fat accumulation in the liver without weight gain. Biochem Biophys Rep 2024; 40:101848. [PMID: 39498441 PMCID: PMC11532936 DOI: 10.1016/j.bbrep.2024.101848] [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] [Received: 01/19/2024] [Revised: 08/02/2024] [Accepted: 10/13/2024] [Indexed: 11/07/2024] Open
Abstract
This study investigated whether a standard calorie diet that is high in glucose and deficient in dietary fibre (described as HGD [high glucose diet]) induces hepatic fat accumulation in mice. We evaluated hepatic steatosis at 7 days and 14 days after the commencement of the HGD. Hepatic triglycerides and areas of oil droplets increased in the HGD group both at day 7 and day 14, whereas weight gain, weight of epididymal fat, and plasma levels of triglycerides were unaffected by HGD consumption. A microarray analysis of the livers revealed that the expression of lipogenesis-related genes was the most affected by HGD consumption. Furthermore, HGD consumption induced the expression of hepatic proteins of fatty acid synthetase, acetyl-CoA carboxylase alpha, and stearoyl-CoA desaturase 1, which are known to be involved in the synthesis of triglyceride. These results indicate that HGD consumption causes fat accumulation in the liver, with an increase in enzymes that are involved in de novo lipogenesis without an accompanying weight or obesity phenotype. Our new findings suggest that HGD consumption could serve as a breeding ground for liver steatosis.
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Affiliation(s)
- Sonoko Karino
- Department of Pharmacology, Faculty of Medicine, Shimane University, Izumo, Shimane, 693-8501, Japan
- Department of Pharmacy, Shimane University Hospital, Izumo, Shimane, 693-8501, Japan
| | - Haruki Usuda
- Department of Pharmacology, Faculty of Medicine, Shimane University, Izumo, Shimane, 693-8501, Japan
| | - Shoma Kanda
- Department of Pharmacology, Faculty of Medicine, Shimane University, Izumo, Shimane, 693-8501, Japan
- Department of Pharmacy, Shimane University Hospital, Izumo, Shimane, 693-8501, Japan
| | - Takayuki Okamoto
- Department of Pharmacology, Faculty of Medicine, Shimane University, Izumo, Shimane, 693-8501, Japan
| | - Tomomi Niibayashi
- Department of Pharmacology, Faculty of Medicine, Shimane University, Izumo, Shimane, 693-8501, Japan
| | - Takahisa Yano
- Department of Pharmacology, Faculty of Medicine, Shimane University, Izumo, Shimane, 693-8501, Japan
- Department of Pharmacy, Shimane University Hospital, Izumo, Shimane, 693-8501, Japan
| | - Kohji Naora
- Department of Pharmacology, Faculty of Medicine, Shimane University, Izumo, Shimane, 693-8501, Japan
- Department of Pharmacy, Shimane University Hospital, Izumo, Shimane, 693-8501, Japan
| | - Koichiro Wada
- Department of Pharmacology, Faculty of Medicine, Shimane University, Izumo, Shimane, 693-8501, Japan
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Weston WC, Hales KH, Hales DB. Utilizing Flaxseed as an Antimicrobial Alternative in Chickens: Integrative Review for Salmonella enterica and Eimeria. Curr Issues Mol Biol 2024; 46:12322-12342. [PMID: 39590326 PMCID: PMC11592616 DOI: 10.3390/cimb46110732] [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: 10/01/2024] [Accepted: 10/24/2024] [Indexed: 11/28/2024] Open
Abstract
This review provides an integrative framework for understanding flaxseed (Linum utassitissimum) as an antimicrobial alternative for poultry production. We begin by familiarizing the reader with the global legislation of antibiotics in animal husbandry; highlighting gaps and current issues for Salmonella enterica (S. enterica) and Eimeria (coccidiosis-inducing). We then discuss the natural, symbiotic characteristics of the Galliformes order (chicken-like birds) and Linum (the flaxes). The key immunological themes in this review include: (i) flaxseed's regulation of innate and adaptive immunity in chickens, (ii) flaxseed's ability to accelerate chicken recovery from infection with S. enterica and Eimeria, and (iii) flaxseed's strengthening of immunity via vitamin B6 antagonism. Research indicates that whole flaxseed increases adaptive immune capacity by augmenting cecal Bacteroides and short-chain fatty acids while also attenuating the heterophil to lymphocyte ratio in chickens. Moreover, flaxseed accelerates chicken recovery from infection with Salmonella Enteritidis or Eimeria tenella; however, future work is needed to better understand (i) defatted flaxseed's superior performance against Eimeria species and (ii) Eimeria maxima's resilience against whole flaxseed. In the context of vitamin B6 antagonism, we propose that 15% whole flaxseed overcomes S. enterica's insult to estrogen synthesis by sustaining the activity of phosphatidylethanolamine methyltransferase (PEMT) in liver. We also propose that 10% defatted flaxseed (as a metformin homologue) strengthens chicken immunity by safeguarding gonadal physiology and by increasing plasma thymidine bioavailability. The concepts in this review can be used as a template for conducting advanced immunological studies in poultry science.
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Affiliation(s)
- William C. Weston
- Department of Molecular, Cellular & Systemic Physiology, School of Medicine, Southern Illinois University, Carbondale, IL 62901, USA;
| | - Karen H. Hales
- Department of Obstetrics & Gynecology, School of Medicine, Southern Illinois University, Carbondale, IL 62901, USA;
| | - Dale B. Hales
- Department of Molecular, Cellular & Systemic Physiology, School of Medicine, Southern Illinois University, Carbondale, IL 62901, USA;
- Department of Obstetrics & Gynecology, School of Medicine, Southern Illinois University, Carbondale, IL 62901, USA;
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Zhu L, Du J, Dai Y, Shen Y, Li H, Zhang Q, Zhao Q, Zhang Q, Ye X, Qin L, Zhang Q. Morinda officinalis iridoid glycosides alleviate methotrexate-induced liver injury in CIA rats by increasing liver autophagy and improving lipid metabolism homeostasis. JOURNAL OF ETHNOPHARMACOLOGY 2024; 333:118486. [PMID: 38914148 DOI: 10.1016/j.jep.2024.118486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 06/18/2024] [Accepted: 06/20/2024] [Indexed: 06/26/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Morinda officinalis How. is a commonly used traditional Chinese herb with the pharmacological properties of tonifying liver and kidney, and enhancing bone and muscle. Iridoid glycosides are the predominant components of this plant, including monotropein, asperuloside, deacetylasperuloside and deacetylasperulosidic acid with their contents reaching more than 2%. Methotrexate (MTX) is the drug of choice for the treatment of rheumatoid arthritis (RA), but liver injury induced by MTX limits its wider use for RA. Morindaofficinalis iridoid glycoside (MOIG) is reported as having anti-RA and hepatoprotective effects, but the exact efficacy on MTX-induced liver injury and the underlying molecular mechanism remain unclear. AIM To elucidate the mitigating effect of MOIG against liver injury in RA rats treated with MTX, and explore the possible mechanism. MATERIALS AND METHODS The effect and mechanism of MOIG were investigated in Wistar rats with collagen-induced arthritis (CIA) which were then treated with MTX, and MTX-induced hepatocyte injury in vitro. Network pharmacological and transcriptomic analyses were conducted to predict the possible mechanisms of MOIG in mitigating MTX-induced liver injury, and lipidomic analysis was performed to further verify the regulatory effects of MOIG on lipid metabolism. BRL-3A hepatocytes were used to evaluate the regulatory effects of MOIG against MTX-associated liver injury. RESULTS MOIG treatment enhanced the anti-RA effect of MTX, and mitigated oxidative damage, inflammation and apoptosis of liver tissues in CIA rats treated with MTX. Network pharmacological and transcriptomic analyses demonstrated that MOIG attenuated liver injury by regulating autophagy and lipid metabolism. The result of lipidomic analysis showed that MOIG reversed the disturbance of lipid metabolism of the liver tissue in CIA rats after MTX treatment. In addition, MOIG also inhibited the apoptosis, reduced the levels of lactate dehydrogenase (LDH), aspartate aminotransferase (ALT) and alanine aminotransferase (AST), regulated oxidative stress, and increased the formation of autophagosome and translocation of LC3 in the nucleus and expression of autophagy regulatory genes Beclin-1, ATG5, LC3Ⅱ, ATG7 and ATG12 in hepatocytes subjected to MTX damage. CONCLUSION Our findings demonstrated that MOIG could ameliorate MTX-induced liver injury in the treatment of RA through increasing hepatocyte autophagy and improving lipid metabolism homeostasis.
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Affiliation(s)
- Lulin Zhu
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China; Department of Pharmacy, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, 310006, China
| | - Jinman Du
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Yuanyuan Dai
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Yi Shen
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Heming Li
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Quanlong Zhang
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Qiming Zhao
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Qi Zhang
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Xinyuan Ye
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Luping Qin
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
| | - Qiaoyan Zhang
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
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Tabone T, Mooney P, Donnellan C. Intestinal failure-associated liver disease: Current challenges in screening, diagnosis, and parenteral nutrition considerations. Nutr Clin Pract 2024; 39:1003-1025. [PMID: 38245851 DOI: 10.1002/ncp.11116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 12/19/2023] [Accepted: 12/25/2023] [Indexed: 01/22/2024] Open
Abstract
Intestinal failure-associated liver disease (IFALD) is a serious life-limiting complication that can occur throughout the clinical course of intestinal failure and its management by parenteral nutrition (PN). Despite this, there is a lack of a standardized definition for IFALD, which makes this insidious condition increasingly difficult to screen and diagnose in clinical practice. Attenuating the progression of liver disease before the onset of liver failure is key to improving morbidity and mortality in these patients. This requires timely detection and promptly addressing reversible factors. Although there are various noninvasive tools available to the clinician to detect early fibrosis or cirrhosis in various chronic liver disease states, these have not been validated in the patient population with IFALD. Such tools include biochemical composite scoring systems for fibrosis, transient elastography, and dynamic liver function tests. This review article aims to highlight the existing real need for an accurate, reproducible method to detect IFALD in its early stages. In addition, we also explore the role PN plays in the pathogenesis of this complex multifactorial condition. Various aspects of PN administration have been implicated in the etiology of IFALD, including the composition of the lipid component, nutrient excess and deficiency, and infusion timing. We aim to highlight the clinical relevance of these PN-associated factors in the development of IFALD and how these can be managed to mitigate the progression of IFALD.
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Affiliation(s)
- Trevor Tabone
- Department of Gastroenterology, St James University Hospital, Leeds, United Kingdom
| | - Peter Mooney
- Department of Gastroenterology, St James University Hospital, Leeds, United Kingdom
| | - Clare Donnellan
- Department of Gastroenterology, St James University Hospital, Leeds, United Kingdom
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Sun B, Ding X, Tan J, Zhang J, Chu X, Zhang S, Liu S, Zhao Z, Xuan S, Xin Y, Zhuang L. TM6SF2 E167K variant decreases PNPLA3-mediated PUFA transfer to promote hepatic steatosis and injury in MASLD. Clin Mol Hepatol 2024; 30:863-882. [PMID: 39054606 PMCID: PMC11540376 DOI: 10.3350/cmh.2024.0268] [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: 04/16/2024] [Revised: 07/05/2024] [Accepted: 07/26/2024] [Indexed: 07/27/2024] Open
Abstract
BACKGROUNDS/AIMS Transmembrane 6 superfamily member 2 (TM6SF2) E167K variant is closely associated with the occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the role and mechanism of TM6SF2 E167K variant during MASLD progression are not yet fully understood. METHODS The Tm6sf2167K knock-in (KI) mice were subjected to high-fat diet (HFD). Hepatic lipid levels of Tm6sf2167K KI mice were detected by lipidomics analysis. Thin-layer chromatography (TLC) was used to measure the newly synthesized triglyceride (TG) and phosphatidylcholine (PC). RESULTS The TM6SF2 E167K variant significantly aggravated hepatic steatosis and injury in HFD-induced mice. Decreased polyunsaturated PC level and increased polyunsaturated TG level were found in liver tissue of HFD-induced Tm6sf2167K KI mice. Mechanistic studies demonstrated that the TM6SF2 E167K variant increased the interaction between TM6SF2 and PNPLA3, and impaired PNPLA3-mediated transfer of polyunsaturated fatty acids (PUFAs) from TG to PC. The TM6SF2 E167K variant increased the level of fatty acid-induced malondialdehyde and reactive oxygen species, and decreased fatty acid-downregulated cell membrane fluidity. Additionally, the TM6SF2 E167K variant decreased the level of hepatic PC containing C18:3, and dietary supplementation of PC containing C18:3 significantly attenuated the TM6SF2 E167K-induced hepatic steatosis and injury in HFD-fed mice. CONCLUSION The TM6SF2 E167K variant could promote its interaction with PNPLA3 and inhibit PNPLA3-mediated transfer of PUFAs from TG to PC, resulting in the hepatic steatosis and injury during MASLD progression. PC containing C18:3 could act as a potential therapeutic supplement for MASLD patients carrying the TM6SF2 E167K variant.
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Affiliation(s)
- Baokai Sun
- Department of Infectious Diseases, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Xiaoqian Ding
- Department of Infectious Diseases, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Jie Tan
- Department of Infectious Diseases, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Jie Zhang
- Department of Infectious Diseases, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Xueru Chu
- Department of Infectious Diseases, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Shuimi Zhang
- Department of Infectious Diseases, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Shousheng Liu
- Clinical Research Center, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Zhenzhen Zhao
- Clinical Research Center, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Shiying Xuan
- Department of Infectious Diseases, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Yongning Xin
- Department of Infectious Diseases, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Likun Zhuang
- Central Laboratories, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
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Su GM, Guo QW, Shen YL, Cai JJ, Chen X, Lin J, Fang DZ. Association between PEMT rs7946 and blood pressure levels in Chinese adolescents. Blood Press Monit 2024; 29:180-187. [PMID: 38502043 DOI: 10.1097/mbp.0000000000000703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/20/2024]
Abstract
OBJECTIVES This study was to explore blood pressure levels in Chinese adolescents with different genotypes of phosphatidylethanolamine N-methyltransferase (PEMT) gene ( PEMT ) rs7946, as well as effects of dietary intake on blood pressure levels with different genders and different genotypes of PEMT rs7946. METHODS PEMT rs7946 genotypes were identified by PCR-restriction fragment length polymorphism and verified by DNA sequencing. Blood pressure was measured using a standard mercury sphygmomanometer. Dietary intakes were analyzed based on a 3-day diet diary, and dietary components were calculated using computer software. RESULTS A total of 721 high school students (314 males and 407 females) at the age of 16.86 ± 0.59 years were included. The A allele carriers of PEMT rs7946 had increased levels of SBP, DBP, mean arterial pressure (MAP) and pulse pressure (PP) than the GG homozygotes in the female subjects. There were significant interactions between PEMT rs7946 and gender on SBP and MAP levels, regardless of whether an unadjusted or adjusted model was used. When dietary intake was taken into account, fat intake was positively associated with SBP and PP in the male GG homozygotes, while protein intake was positively associated with PP in the female A allele carriers of PEMT rs7946. CONCLUSION This study suggests that PEMT rs7946 is significantly associated with blood pressure levels in human being. There might be interactions among PEMT rs7946, gender, and dietary intake on blood pressure levels in the adolescent population.
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Affiliation(s)
- Guo Ming Su
- Department of Biochemistry and Molecular Biology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China
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Arshad U, Santos JEP. Graduate Student Literature Review: Exploring choline's important roles as a nutrient for transition dairy cows. J Dairy Sci 2024; 107:4357-4369. [PMID: 38522836 DOI: 10.3168/jds.2023-24050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 01/22/2024] [Indexed: 03/26/2024]
Abstract
In late gestation and in the first weeks postpartum, lipid droplets accumulate in the hepatic tissue resulting in approximately 40% to 50% of the dairy cows developing hepatic lipidosis in the first weeks of lactation. Elevated concentrations of triacylglycerol in the hepatic tissue are associated with increased risk of peripartum diseases and impaired productive performance. Cows with hepatic lipidosis need to dispose the excess of hepatic triacylglycerol, but this is a slow process in the bovine liver and relies on primary mechanisms such as complete oxidation and ketogenesis because of the limited export of triacylglycerols as lipoproteins. Choline is a lipotropic compound because, among other functions, it facilitates the export of lipids from the liver. Supplementing choline as rumen-protected choline (RPC) to diets of feed-restricted dairy cows reduces the degree of triacylglycerol infiltration into the hepatic parenchyma in part by enhancing export of triacylglycerol as nascent lipoprotein. The reduced accumulation of triacylglycerol in hepatic tissue in feed-restricted cows fed RPC might affect secondary pathways involved in hepatic disposal of fatty acids such as increased cellular autophagy and lipophagy and minimize endoplasmic reticulum stress response and hepatocyte inflammation. Collectively, these effects on secondary pathways might further reduce the severity of hepatic lipidosis in cows. One of the benefits of supplementing RPC is improved fat digestibility, perhaps because choline, through phosphatidylcholines, facilitates lipid transport within the enterocyte by increasing the synthesis of chylomicrons. Finally, when supplemented during the transition period, RPC improves productive performance of cows, irrespective of their body condition, that extends well beyond the period of supplementation. This review summarizes the current understanding of hepatic lipidosis in early lactation, recapitulates the absorption, transport and metabolism of choline, and discusses its role on hepatic metabolism and gastrointestinal functions, which collectively results in improved performance in dairy cows.
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Affiliation(s)
- U Arshad
- Department of Animal Sciences, University of Florida, Gainesville, FL 32611; Department of Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, WI 53706.
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11
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Popov J, Despot T, Avelar Rodriguez D, Khan I, Mech E, Khan M, Bojadzija M, Pai N. Implications of Microbiota and Immune System in Development and Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease. Nutrients 2024; 16:1668. [PMID: 38892602 PMCID: PMC11175128 DOI: 10.3390/nu16111668] [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: 05/10/2024] [Revised: 05/23/2024] [Accepted: 05/27/2024] [Indexed: 06/21/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent type of liver disease worldwide. The exact pathophysiology behind MASLD remains unclear; however, it is thought that a combination of factors or "hits" act as precipitants for disease onset and progression. Abundant evidence supports the roles of diet, genes, metabolic dysregulation, and the intestinal microbiome in influencing the accumulation of lipids in hepatocytes and subsequent progression to inflammation and fibrosis. Currently, there is no cure for MASLD, but lifestyle changes have been the prevailing cornerstones of management. Research is now focusing on the intestinal microbiome as a potential therapeutic target for MASLD, with the spotlight shifting to probiotics, antibiotics, and fecal microbiota transplantation. In this review, we provide an overview of how intestinal microbiota interact with the immune system to contribute to the pathogenesis of MASLD and metabolic dysfunction-associated steatohepatitis (MASH). We also summarize key microbial taxa implicated in the disease and discuss evidence supporting microbial-targeted therapies in its management.
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Affiliation(s)
- Jelena Popov
- Boston Combined Residency Program, Boston Children’s Hospital & Boston Medical Center, Boston, MA 02115, USA;
| | - Tijana Despot
- College of Medicine and Health, University College Cork, T12 YN60 Cork, Ireland; (T.D.); (I.K.)
| | - David Avelar Rodriguez
- Department of Pediatric Gastroenterology, Hepatology & Nutrition, The Hospital for Sick Children, University of Toronto, Toronto, ON M5G 1E8, Canada;
| | - Irfan Khan
- College of Medicine and Health, University College Cork, T12 YN60 Cork, Ireland; (T.D.); (I.K.)
| | - Eugene Mech
- School of Medicine, University College Dublin, D04 C1P1 Dublin, Ireland;
| | - Mahrukh Khan
- Department of Pediatrics, Faculty of Health Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada;
- Department of Medical Sciences, Faculty of Health Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada
| | - Milan Bojadzija
- Department of Internal Medicine, Subotica General Hospital, 24000 Subotica, Serbia;
| | - Nikhil Pai
- Department of Pediatrics, Faculty of Health Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada;
- Division of Gastroenterology, Hepatology and Nutrition, McMaster Children’s Hospital, Hamilton, ON L8S 4L8, Canada
- Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
- Division of Gastroenterology, Hepatology, and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
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12
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Luo T, Jiang X, Xu N, Zhao X, Xie X, Xia X, Bian X, Liu H. Risk factors and metabolomics of mild cognitive impairment in type 2 diabetes mellitus. Front Mol Biosci 2024; 11:1341290. [PMID: 38698772 PMCID: PMC11063278 DOI: 10.3389/fmolb.2024.1341290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 04/08/2024] [Indexed: 05/05/2024] Open
Abstract
Objective: This study aimed to explore the risk factors, metabolic characteristics, and potential biomarkers of mild cognitive impairment in type 2 diabetes mellitus (T2DM-MCI) and to provide potential evidence for the diagnosis, prevention, and treatment of mild cognitive impairment (MCI) in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 103 patients with T2DM were recruited from the Endocrinology Department of The Second Affiliated Hospital of Dalian Medical University for inclusion in the study. The Montreal Cognitive Assessment (MoCA) was utilized to evaluate the cognitive functioning of all patients. Among them, 50 patients were categorized into the T2DM-MCI group (MoCA score < 26 points), while 53 subjects were classified into the T2DM without cognitive impairment (T2DM-NCI) group (MoCA score ≥ 26 points). Serum samples were collected from the subjects, and metabolomics profiling data were generated by Ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS). These groups were analyzed to investigate the differences in expression of small molecule metabolites, metabolic pathways, and potential specific biomarkers. Results: Comparison between the T2DM-MCI group and T2DM-NCI group revealed significant differences in years of education, history of insulin application, insulin resistance index, insulin-like growth factor-binding protein-3 (IGFBP-3), and creatinine levels. Further binary logistic regression analysis of the variables indicated that low educational level and low serum IGFBP-3 were independent risk factor for T2DM-MCI. Metabolomics analysis revealed that differential expression of 10 metabolites between the T2DM-MCI group and T2DM-NCI group (p < 0.05 and FDR<0.05, VIP>1.5). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analysis revealed that fatty acid degradation was the most significant pathway. Receiver operating characteristic (ROC) analysis shows that lysophosphatidylcholine (LPC) 18:0 exhibited greater diagnostic efficiency. Conclusion: This study revealed that a shorter duration of education and lower serum IGFBP-3 levels are independent risk factors for T2DM-MCI. Serum metabolites were found to be altered in both T2DM-MCI and T2DM-NCI groups. T2DM patients with or without MCI can be distinguished by LPC 18:0. Abnormal lipid metabolism plays a significant role in the development of MCI in T2DM patients.
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Affiliation(s)
- Tao Luo
- Endocrinology and Metabolism Department, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Xiao Jiang
- Endocrinology and Metabolism Department, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Ning Xu
- Endocrinology Department, The Second Hospital of Chao Yang, Chaoyang, China
| | - Xinyu Zhao
- Endocrinology and Metabolism Department, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Xingjie Xie
- Endocrinology and Metabolism Department, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Xiuwen Xia
- Endocrinology and Metabolism Department, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - XiaoLong Bian
- The Second Clinical College, Dalian Medical University, Dalian, China
| | - Haixia Liu
- Endocrinology and Metabolism Department, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
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Blázquez-García I, Guerrero L, Cacho-Navas C, Djouder N, Millan J, Paradela A, Carmona-Rodríguez L, Corrales FJ. Molecular Insights of Cholestasis in MDR2 Knockout Murine Liver Organoids. J Proteome Res 2024; 23:1433-1442. [PMID: 38488493 PMCID: PMC11002922 DOI: 10.1021/acs.jproteome.3c00900] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 02/29/2024] [Accepted: 03/06/2024] [Indexed: 04/06/2024]
Abstract
MDR3 (multidrug resistance 3) deficiency in humans (MDR2 in mice) causes progressive familial intrahepatic cholestasis type 3 (PFIC3). PFIC3 is a lethal disease characterized by an early onset of intrahepatic cholestasis progressing to liver cirrhosis, a preneoplastic condition, putting individuals at risk of hepatocellular carcinoma (HCC). Hepatocyte-like organoids from MDR2-deficient mice (MDR2KO) were used in this work to study the molecular alterations caused by the deficiency of this transporter. Proteomic analysis by mass spectrometry allowed characterization of 279 proteins that were differentially expressed in MDR2KO compared with wild-type organoids. Functional enrichment analysis indicated alterations in three main cellular functions: (1) interaction with the extracellular matrix, (2) remodeling intermediary metabolism, and (3) cell proliferation and differentiation. The affected cellular processes were validated by orthogonal molecular biology techniques. Our results point to molecular mechanisms associated with PFIC3 that may drive the progression to liver cirrhosis and HCC and suggest proteins and cellular processes that could be targeted for the development of early detection strategies for these severe liver diseases.
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Affiliation(s)
- Irene Blázquez-García
- Functional
Proteomics Laboratory, Centro Nacional de
Biotecnología (CSIC), Madrid 28049, Spain
| | - Laura Guerrero
- Functional
Proteomics Laboratory, Centro Nacional de
Biotecnología (CSIC), Madrid 28049, Spain
| | | | - Nabil Djouder
- Centro
Nacional de Investigaciones Oncológicas (CNIO), Madrid 28029, Spain
| | - Jaime Millan
- Centro
de Biología Molecular Severo Ochoa (CBMSO), Madrid 28049, Spain
| | - Alberto Paradela
- Functional
Proteomics Laboratory, Centro Nacional de
Biotecnología (CSIC), Madrid 28049, Spain
| | | | - Fernando J. Corrales
- Functional
Proteomics Laboratory, Centro Nacional de
Biotecnología (CSIC), Madrid 28049, Spain
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Bahitham W, Alghamdi S, Omer I, Alsudais A, Hakeem I, Alghamdi A, Abualnaja R, Sanai FM, Rosado AS, Sergi CM. Double Trouble: How Microbiome Dysbiosis and Mitochondrial Dysfunction Drive Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis. Biomedicines 2024; 12:550. [PMID: 38540163 PMCID: PMC10967987 DOI: 10.3390/biomedicines12030550] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 02/12/2024] [Accepted: 02/18/2024] [Indexed: 11/22/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are closely related liver conditions that have become more prevalent globally. This review examines the intricate interplay between microbiome dysbiosis and mitochondrial dysfunction in the development of NAFLD and NASH. The combination of these two factors creates a synergistic situation referred to as "double trouble", which promotes the accumulation of lipids in the liver and the subsequent progression from simple steatosis (NAFLD) to inflammation (NASH). Microbiome dysbiosis, characterized by changes in the composition of gut microbes and increased intestinal permeability, contributes to the movement of bacterial products into the liver. It triggers metabolic disturbances and has anti-inflammatory effects. Understanding the complex relationship between microbiome dysbiosis and mitochondrial dysfunction in the development of NAFLD and NASH is crucial for advancing innovative therapeutic approaches that target these underlying mechanisms.
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Affiliation(s)
- Wesam Bahitham
- King Abdullah International Medical Research Center-WR, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard for Health Affairs, Riyadh 11426, Saudi Arabia; (W.B.); (S.A.); (I.O.); (A.A.); (I.H.); (A.A.); (R.A.)
- Bioscience, Biological and Environmental Sciences and Engineering Division (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955, Saudi Arabia;
| | - Siraj Alghamdi
- King Abdullah International Medical Research Center-WR, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard for Health Affairs, Riyadh 11426, Saudi Arabia; (W.B.); (S.A.); (I.O.); (A.A.); (I.H.); (A.A.); (R.A.)
| | - Ibrahim Omer
- King Abdullah International Medical Research Center-WR, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard for Health Affairs, Riyadh 11426, Saudi Arabia; (W.B.); (S.A.); (I.O.); (A.A.); (I.H.); (A.A.); (R.A.)
| | - Ali Alsudais
- King Abdullah International Medical Research Center-WR, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard for Health Affairs, Riyadh 11426, Saudi Arabia; (W.B.); (S.A.); (I.O.); (A.A.); (I.H.); (A.A.); (R.A.)
| | - Ilana Hakeem
- King Abdullah International Medical Research Center-WR, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard for Health Affairs, Riyadh 11426, Saudi Arabia; (W.B.); (S.A.); (I.O.); (A.A.); (I.H.); (A.A.); (R.A.)
| | - Arwa Alghamdi
- King Abdullah International Medical Research Center-WR, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard for Health Affairs, Riyadh 11426, Saudi Arabia; (W.B.); (S.A.); (I.O.); (A.A.); (I.H.); (A.A.); (R.A.)
| | - Reema Abualnaja
- King Abdullah International Medical Research Center-WR, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard for Health Affairs, Riyadh 11426, Saudi Arabia; (W.B.); (S.A.); (I.O.); (A.A.); (I.H.); (A.A.); (R.A.)
| | - Faisal M. Sanai
- Gastroenterology Unit, Department of Medicine, King Abdulaziz Medical City, Jeddah 21423, Saudi Arabia;
| | - Alexandre S. Rosado
- Bioscience, Biological and Environmental Sciences and Engineering Division (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955, Saudi Arabia;
| | - Consolato M. Sergi
- Anatomic Pathology, Children’s Hospital of Eastern Ontario (CHEO), University of Ottawa, Ottawa, ON K1N 6N5, Canada
- Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 2B7, Canada
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15
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Hu J, Dai J, Sheng N. Kynurenic Acid Plays a Protective Role in Hepatotoxicity Induced by HFPO-DA in Male Mice. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2024; 58:1842-1853. [PMID: 38228288 DOI: 10.1021/acs.est.3c08033] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/18/2024]
Abstract
Following its introduction as an alternative to perfluorooctanoic acid, hexafluoropropylene oxide dimer acid (HFPO-DA) has been extensively detected in various environmental matrices. Despite this prevalence, limited information is available regarding its hepatotoxicity biomarkers. In this study, toxicokinetic simulations indicated that under repeated treatment, HFPO-DA in mice serum reached a steady state by the 4th day. To assess its subacute hepatic effects and identify potential biomarkers, mice were administered HFPO-DA orally at doses of 0, 0.1, 0.5, 2.5, 12.5, or 62.5 mg/kg/d for 7 d. Results revealed that the lowest observed adverse effect levels were 0.5 mg/kg/d for hepatomegaly and 2.5 mg/kg/d for hepatic injury. Serum metabolomics analysis identified 34, 58, and 118 differential metabolites in the 0.1, 0.5, and 2.5 mg/kg/d groups, respectively, compared to the control group. Based on weighted gene coexpression network analysis, eight potential hepatotoxicity-related metabolites were identified; among them, kynurenic acid (KA) in mouse serum exhibited the highest correlation with liver injury. Furthermore, liver-targeted metabolomics analysis demonstrated that HFPO-DA exposure induced metabolic migration of the kynurenine pathway from KA to nicotinamide adenine dinucleotide, resulting in the activation of endoplasmic reticulum stress and the nuclear factor kappa-B signaling pathway. Notably, pretreatment with KA significantly attenuated liver injury induced by HFPO-DA exposure in mice, highlighting the pivotal roles of KA in the hepatotoxicity of HFPO-DA.
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Affiliation(s)
- Jianglin Hu
- State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants, School of Environmental Science and Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Minhang District, Shanghai 200240, China
| | - Jiayin Dai
- State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants, School of Environmental Science and Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Minhang District, Shanghai 200240, China
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China
| | - Nan Sheng
- State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants, School of Environmental Science and Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Minhang District, Shanghai 200240, China
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16
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Jung IR, Ahima RS, Kim SF. Time-Restricted Feeding Ameliorates Methionine-Choline Deficient Diet-Induced Steatohepatitis in Mice. Int J Mol Sci 2024; 25:1390. [PMID: 38338668 PMCID: PMC10855189 DOI: 10.3390/ijms25031390] [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: 12/04/2023] [Revised: 01/20/2024] [Accepted: 01/21/2024] [Indexed: 02/12/2024] Open
Abstract
Non-alcoholic steatohepatitis (NASH) is an inflammatory form of non-alcoholic fatty liver disease (NAFLD), closely associated with disease progression, cirrhosis, liver failure, and hepatocellular carcinoma. Time-restricted feeding (TRF) has been shown to decrease body weight and adiposity and improve metabolic outcomes; however, the effect of TRF on NASH has not yet been fully understood. We had previously reported that inositol polyphosphate multikinase (IPMK) mediates hepatic insulin signaling. Importantly, we have found that TRF increases hepatic IPMK levels. Therefore, we investigated whether there is a causal link between TRF and IPMK in a mouse model of NASH, i.e., methionine- and choline-deficient diet (MCDD)-induced steatohepatitis. Here, we show that TRF alleviated markers of NASH, i.e., reduced hepatic steatosis, liver triglycerides (TG), serum alanine transaminase (ALT) and aspartate aminotransferase (AST), inflammation, and fibrosis in MCDD mice. Interestingly, MCDD led to a significant reduction in IPMK levels, and the deletion of hepatic IPMK exacerbates the NASH phenotype induced by MCDD, accompanied by increased gene expression of pro-inflammatory chemokines. Conversely, TRF restored IPMK levels and significantly reduced gene expression of proinflammatory cytokines and chemokines. Our results demonstrate that TRF attenuates MCDD-induced NASH via IPMK-mediated changes in hepatic steatosis and inflammation.
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Affiliation(s)
| | - Rexford S. Ahima
- Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Johns Hopkins University, Baltimore, MD 21218, USA;
| | - Sangwon F. Kim
- Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Johns Hopkins University, Baltimore, MD 21218, USA;
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Sha Y, Liu X, Pu X, He Y, Wang J, Zhao S, Shao P, Wang F, Xie Z, Chen X, Yang W. Characterizing the dynamics of the rumen microbiota, its metabolites, and blood metabolites across reproductive stages in Small-tailed Han sheep. Microbiol Spectr 2023; 11:e0286723. [PMID: 37948319 PMCID: PMC10715166 DOI: 10.1128/spectrum.02867-23] [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: 07/17/2023] [Accepted: 10/23/2023] [Indexed: 11/12/2023] Open
Abstract
IMPORTANCE Our study illustrates the succession of the rumen microbiota and its metabolites in Small-tailed Han sheep at different reproductive stages. Among them, Firmicutes and Prevotella, which are related to energy metabolism, increased in abundance during pregnancy, while Fibrobacter, a fiber-degrading bacterium, increased in abundance during lactation. At the same time, the microbial metabolic profile and serum metabolic profile characteristics of different reproductive stages were revealed, and some functional pathways and metabolites related to energy and immunity were found. This study provides a reference for the health management of ruminants during non-pregnancy, pregnancy, and lactation.
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Affiliation(s)
- Yuzhu Sha
- College of Animal Science and Technology/Gansu Key Laboratory of Herbivorous Animal Biotechnology, Gansu Agricultural University, Lanzhou, China
| | - Xiu Liu
- College of Animal Science and Technology/Gansu Key Laboratory of Herbivorous Animal Biotechnology, Gansu Agricultural University, Lanzhou, China
| | - Xiaoning Pu
- College of Animal Science and Technology/Gansu Key Laboratory of Herbivorous Animal Biotechnology, Gansu Agricultural University, Lanzhou, China
| | - Yanyu He
- School of Fundamental Sciences, Massey University, Palmerston North, New Zealand
| | - Jiqing Wang
- College of Animal Science and Technology/Gansu Key Laboratory of Herbivorous Animal Biotechnology, Gansu Agricultural University, Lanzhou, China
| | - Shengguo Zhao
- College of Animal Science and Technology/Gansu Key Laboratory of Herbivorous Animal Biotechnology, Gansu Agricultural University, Lanzhou, China
| | - Pengyang Shao
- College of Animal Science and Technology/Gansu Key Laboratory of Herbivorous Animal Biotechnology, Gansu Agricultural University, Lanzhou, China
| | - Fanxiong Wang
- College of Animal Science and Technology/Gansu Key Laboratory of Herbivorous Animal Biotechnology, Gansu Agricultural University, Lanzhou, China
| | - Zhuanhui Xie
- College of Animal Science and Technology/Gansu Key Laboratory of Herbivorous Animal Biotechnology, Gansu Agricultural University, Lanzhou, China
| | - Xiaowei Chen
- College of Animal Science and Technology/Gansu Key Laboratory of Herbivorous Animal Biotechnology, Gansu Agricultural University, Lanzhou, China
| | - Wenxin Yang
- College of Animal Science and Technology/Gansu Key Laboratory of Herbivorous Animal Biotechnology, Gansu Agricultural University, Lanzhou, China
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Wang L, Yu X, Li H, He D, Zeng S, Xiang Z. Cell and rat serum, urine and tissue metabolomics analysis elucidates the key pathway changes associated with chronic nephropathy and reveals the mechanism of action of rhein. Chin Med 2023; 18:158. [PMID: 38041193 PMCID: PMC10691122 DOI: 10.1186/s13020-023-00862-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Accepted: 11/21/2023] [Indexed: 12/03/2023] Open
Abstract
BACKGROUND Rhein can significantly delay the progression of chronic nephropathy. However, its mechanism of action has not been adequately elaborated, which hinders its extensive clinical application. In this work, the effects of rhein on models of TGF-β-induced NRK-49F cellular fibrosis and rat renal ischemia-reperfusion fibrosis were evaluated using metabolomics and western blotting. METHODS The metabolic profiles of NRK-49F cells and rat urine, serum, and kidney tissues in the control, model, and rhein groups were investigated using UPLC-QTOF-MS. The levels of p-P65, p-IKK, p-AKT, p-P38, p-JNK and AP-1 in NRK-49F cells were measured using western blotting and immunofluorescence methods. Molecular docking and network pharmacology methods were employed to explore the relationship between the potential targets of rhein and key proteins in the NF-κB and MAPK signaling pathways. RESULTS Various potential metabolites, including sphingolipids, ceramides, phosphatidylcholine, and lysophosphatidylcholine,14-hydroxy-E4-neuroprostane E, and 5-HPETE, were present in the cell, tissue, urine, and serum samples; however, few metabolites matches exactly among the four type of biological samples. These differential metabolites can effectively differentiated between the control, model, and rhein groups. Pathway enrichment analysis of differential metabolites unveiled that sphingolipid metabolism, arachidonic acid metabolism, and glycerophospholipid metabolism were closely related to nephropathy. Phosphorylation levels of AKT, IKK, P65 and AP-1 in NRK-49F cells was reduced by rhein treatment. Network pharmacology and molecular docking showed that the potential targets of rhein might regulated the expression of MAPK and AKT in the NF-κB and MAPK signaling pathways. CONCLUSION In brief, rhein might delays the progression of chronic nephropathy via the metabolic pathways, NF-κB and MAPKs signaling pathways, which provides the foundation for its development and clinical application.
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Affiliation(s)
- Li Wang
- Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang, People's Republic of China
- Medical School, Hangzhou City University, Hangzhou, 310015, China
- Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, 310015, China
| | - Xixi Yu
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China
| | - Hongju Li
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310018, China
| | - Dahong He
- Medical School, Hangzhou City University, Hangzhou, 310015, China
| | - Su Zeng
- Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang, People's Republic of China.
| | - Zheng Xiang
- Medical School, Hangzhou City University, Hangzhou, 310015, China.
- Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, 310015, China.
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Chai C, Chen L, Deng MG, Liang Y, Liu F, Nie JQ. Dietary choline intake and non-alcoholic fatty liver disease (NAFLD) in U.S. adults: National Health and Nutrition Examination Survey (NHANES) 2017-2018. Eur J Clin Nutr 2023; 77:1160-1166. [PMID: 37634048 DOI: 10.1038/s41430-023-01336-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 08/15/2023] [Accepted: 08/18/2023] [Indexed: 08/28/2023]
Abstract
BACKGROUND Whether there is an association between dietary choline intake and non-alcoholic fatty liver disease (NAFLD) in American adults remains unclear. METHODS Data came from the National Health and Nutrition Examination Survey 2017-2018. Choline intake was defined by the mean amounts of two 24 h dietary recalls, and choline intake was categorized into three groups according to the quartiles: inadequate ( P75). Hepatic steatosis was assessed with FibroScan®, in which VCTE was employed with controlled attenuation to derive the controlled attenuation parameter (CAP), and NAFLD was defined as a CAP score ≥285 dB/m. Multivariable linear regression was performed to assess the linear relationship between choline intake and CAP. Multivariable logistics regression models were conducted to assess the association between choline intake status and NAFLD in the final sample and subgroup analysis was then performed in men and women. RESULTS The amount of dietary choline was inversely associated with CAP score (β = -0.262, 95% CI: -0.280, -0.245). Compared to inadequate choline intake, optimal choline intake was related to a lower risk of NAFLD (OR: 0.705, 95% CI: 0.704-0.706) in the final sample. Subgroup analysis by gender revealed that the highest choline intake status was associated with a lower risk of NAFLD both in females (OR: 0.764, 95% CI: 0.762-0.766), and males (OR: 0.955, 95% CI: 0.953-0.958) when compared to the lowest choline intake. CONCLUSIONS With the latest NHANES data, we found that higher dietary choline was associated with a lower risk of NAFLD in American adults, and such a relationship exists in both females and males.
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Affiliation(s)
- Chen Chai
- Emergency Center, Hubei Clinical Research Center for Emergency and Resuscitation, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
| | - Lin Chen
- Emergency Department, Xiantao First People's Hospital Affiliated to Changjiang University, Xiantao, China
| | - Ming-Gang Deng
- School of Public Health, Wuhan University, Wuhan, 430071, China
| | - Yuehui Liang
- School of Public Health, Wuhan University, Wuhan, 430071, China
| | - Fang Liu
- School of Public Health, Wuhan University, Wuhan, 430071, China
| | - Jia-Qi Nie
- School of Public Health, Wuhan University, Wuhan, 430071, China
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20
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Xie Z, Du J, Gan M, Zhou C, Li M, Liu C, Wang M, Chen L, Zhao Y, Wang Y, Jiang Y, Cheng W, Zhu K, Luo Y, Zhu L, Shen L. Short-term dietary choline supplementation alters the gut microbiota and liver metabolism of finishing pigs. Front Microbiol 2023; 14:1266042. [PMID: 37840732 PMCID: PMC10569418 DOI: 10.3389/fmicb.2023.1266042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 09/04/2023] [Indexed: 10/17/2023] Open
Abstract
Choline is an essential nutrient for pig development and plays a role in the animal's growth performance, carcass characteristics, and reproduction aspects in weaned pigs and sows. However, the effect of choline on finishing pigs and its potential regulatory mechanism remains unclear. Here, we feed finishing pigs with 1% of the hydrochloride salt of choline, such as choline chloride (CHC), under a basic diet condition for a short period of time (14 days). A 14-day supplementation of CHC significantly increased final weight and carcass weight while having no effect on carcass length, average backfat, or eye muscle area compared with control pigs. Mechanically, CHC resulted in a significant alteration of gut microbiota composition in finishing pigs and a remarkably increased relative abundance of bacteria contributing to growth performance and health, including Prevotella, Ruminococcaceae, and Eubacterium. In addition, untargeted metabolomics analysis identified 84 differently abundant metabolites in the liver between CHC pigs and control pigs, of which most metabolites were mainly enriched in signaling pathways related to the improvement of growth, development, and health. Notably, there was no significant difference in the ability of oxidative stress resistance between the two groups, although increased bacteria and metabolites keeping balance in reactive oxygen species showed in finishing pigs after CHC supplementation. Taken together, our results suggest that a short-term supplementation of CHC contributes to increased body weight gain and carcass weight of finishing pigs, which may be involved in the regulation of gut microbiota and alterations of liver metabolism, providing new insights into the potential of choline-mediated gut microbiota/metabolites in improving growth performance, carcass characteristics, and health.
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Affiliation(s)
- Zhongwei Xie
- Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu, China
- State Key Laboratory of Swine and Poultry Breeding Industry, Sichuan Agricultural University, Chengdu, China
| | - Junhua Du
- Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu, China
- State Key Laboratory of Swine and Poultry Breeding Industry, Sichuan Agricultural University, Chengdu, China
| | - Mailin Gan
- Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu, China
- State Key Laboratory of Swine and Poultry Breeding Industry, Sichuan Agricultural University, Chengdu, China
| | - Chengpeng Zhou
- Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu, China
- State Key Laboratory of Swine and Poultry Breeding Industry, Sichuan Agricultural University, Chengdu, China
| | - Menglin Li
- Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu, China
- State Key Laboratory of Swine and Poultry Breeding Industry, Sichuan Agricultural University, Chengdu, China
| | - Chengming Liu
- Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu, China
- State Key Laboratory of Swine and Poultry Breeding Industry, Sichuan Agricultural University, Chengdu, China
| | - Meng Wang
- Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu, China
- State Key Laboratory of Swine and Poultry Breeding Industry, Sichuan Agricultural University, Chengdu, China
| | - Lei Chen
- Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu, China
- State Key Laboratory of Swine and Poultry Breeding Industry, Sichuan Agricultural University, Chengdu, China
| | - Ye Zhao
- Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu, China
- State Key Laboratory of Swine and Poultry Breeding Industry, Sichuan Agricultural University, Chengdu, China
| | - Yan Wang
- Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu, China
- State Key Laboratory of Swine and Poultry Breeding Industry, Sichuan Agricultural University, Chengdu, China
| | - Yanzhi Jiang
- State Key Laboratory of Swine and Poultry Breeding Industry, Sichuan Agricultural University, Chengdu, China
- College of Life Science, Sichuan Agricultural University, Chengdu, China
| | | | - Kangping Zhu
- Sichuan Dekon Livestock Foodstuff Group, Shuangliu, China
| | - Yi Luo
- Sichuan Dekon Livestock Foodstuff Group, Shuangliu, China
| | - Li Zhu
- Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu, China
- State Key Laboratory of Swine and Poultry Breeding Industry, Sichuan Agricultural University, Chengdu, China
| | - Linyuan Shen
- Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu, China
- State Key Laboratory of Swine and Poultry Breeding Industry, Sichuan Agricultural University, Chengdu, China
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21
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Aggeletopoulou I, Kalafateli M, Tsounis EP, Triantos C. Epigenetic Regulation in Lean Nonalcoholic Fatty Liver Disease. Int J Mol Sci 2023; 24:12864. [PMID: 37629043 PMCID: PMC10454848 DOI: 10.3390/ijms241612864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 08/11/2023] [Accepted: 08/14/2023] [Indexed: 08/27/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD), the most prominent cause of chronic liver disease worldwide, is a rapidly growing epidemic. It consists of a wide range of liver diseases, from steatosis to nonalcoholic steatohepatitis, and predisposes patients to liver fibrosis, cirrhosis, and even hepatocellular carcinoma. NAFLD is strongly correlated with obesity; however, it has been extensively reported among lean/nonobese individuals in recent years. Although lean patients demonstrate a lower prevalence of diabetes mellitus, central obesity, dyslipidemia, hypertension, and metabolic syndrome, a percentage of these patients may develop steatohepatitis, advanced liver fibrosis, and cardiovascular disease, and have increased all-cause mortality. The pathophysiological mechanisms of lean NAFLD remain vague. Studies have reported that lean NAFLD demonstrates a close association with environmental factors, genetic predisposition, and epigenetic modifications. In this review, we aim to discuss and summarize the epigenetic mechanisms involved in lean NAFLD and to introduce the interaction between epigenetic patterns and genetic or non genetic factors. Several epigenetic mechanisms have been implicated in the regulation of lean NAFLD. These include DNA methylation, histone modifications, and noncoding-RNA-mediated gene regulation. Epigenetics is an area of special interest in the setting of lean NAFLD as it could provide new insights into the therapeutic options and noninvasive biomarkers that target this under-recognized and challenging disorder.
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Affiliation(s)
- Ioanna Aggeletopoulou
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece; (I.A.); (E.P.T.)
| | - Maria Kalafateli
- Department of Gastroenterology, General Hospital of Patras, 26332 Patras, Greece;
| | - Efthymios P. Tsounis
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece; (I.A.); (E.P.T.)
| | - Christos Triantos
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece; (I.A.); (E.P.T.)
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22
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Thomaz MS, Sertorio MN, Gazarini ML, Ribeiro DA, Pisani LP, Nagaoka MR. Effect of Kinins on the Hepatic Oxidative Stress in Mice Treated with a Methionine-Choline Deficient Diet. Biomedicines 2023; 11:2199. [PMID: 37626696 PMCID: PMC10452290 DOI: 10.3390/biomedicines11082199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 07/21/2023] [Accepted: 07/26/2023] [Indexed: 08/27/2023] Open
Abstract
Non-alcoholic fatty liver is the leading cause of hepatic disease worldwide and ranges from simple steatosis to non-alcoholic steatohepatitis (NASH) due to cell injury, oxidative stress, and apoptosis. The kinins' role in the liver has been studied in experimental fibrosis, partial hepatectomy, and ischemia-reperfusion and is related to cell death and regeneration. We investigated its role in experimental NASH induced by a methionine-choline deficient diet for 4 weeks. After that, liver perfusion was performed, and bradykinin (BK) or des-Arg9-BK was infused. Cell death was evaluated by cathepsin-B and caspase-3 activity and oxidative stress by catalase (CAT), glutathione S-transferase, and superoxide dismutase (SOD) activities, as well as malondialdehyde and carbonylated proteins. In control livers, DABK increased CAT activity, which was reversed by antagonist DALBK. In the NASH group, kinins tend to decrease antioxidant activity, with SOD activity being significantly reduced by BK and DABK. Malondialdehyde levels increased in all NASH groups, but carbonylated protein did not. DABK significantly decreased cathepsin-B in the NASH group, while caspase-3 was increased by BK in control animals. Our results suggest that B1R and/or B2R activation did not induce oxidative stress but affected the antioxidant system, reducing SOD in the NASH group.
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Affiliation(s)
| | | | | | | | | | - Marcia Regina Nagaoka
- Department of Biosciences, Instituto Saúde Sociedade, Universidade Federal de São Paulo, Santos 11015-020, SP, Brazil; (M.S.T.)
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23
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Warren D, Benedito VA, Skinner RC, Alawadi A, Vendemiatti E, Laub DJ, Showman C, Matak K, Tou JC. Low-Protein Diets Composed of Protein Recovered from Food Processing Supported Growth, but Induced Mild Hepatic Steatosis Compared with a No-Protein Diet in Young Female Rats. J Nutr 2023; 153:1668-1679. [PMID: 36990182 PMCID: PMC10447611 DOI: 10.1016/j.tjnut.2023.03.028] [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: 01/01/2023] [Revised: 03/08/2023] [Accepted: 03/20/2023] [Indexed: 03/29/2023] Open
Abstract
BACKGROUND Living in low-income countries often restricts the consumption of adequate protein and animal protein. OBJECTIVES This study aimed to investigate the effects of feeding low-protein diets on growth and liver health using proteins recovered from animal processing. METHODS Female Sprague-Dawley rats (aged 28 d) were randomly assigned (n = 8 rats/group) to be fed standard purified diets with 0% or 10% kcal protein that was comprised of either carp, whey, or casein. RESULTS Rats that were fed low-protein diets showed higher growth but developed mild hepatic steatosis compared to rats that were fed a no-protein diet, regardless of the protein source. Real-time quantitative polymerase chain reactions targeting the expression of genes involved in liver lipid homeostasis were not significantly different among groups. Global RNA-sequencing technology identified 9 differentially expressed genes linked to folate-mediated 1-carbon metabolism, endoplasmic reticulum (ER) stress, and metabolic diseases. Canonical pathway analysis revealed that mechanisms differed depending on the protein source. ER stress and dysregulated energy metabolism were implicated in hepatic steatosis in carp- and whey-fed rats. In contrast, impaired liver one-carbon methylations, lipoprotein assembly, and lipid export were implicated in casein-fed rats. CONCLUSIONS Carp sarcoplasmic protein showed comparable results to commercially available casein and whey protein. A better understanding of the molecular mechanisms in hepatic steatosis development can assist formulation of proteins recovered from food processing into a sustainable source of high-quality protein.
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Affiliation(s)
- Derek Warren
- Division of Animal and Nutritional Sciences, West Virginia University, Morgantown, WV, United States; Department of Biology, University of the Ozarks, Clarksville, AR, United States
| | - Vagner A Benedito
- Division of Plant and Soil Sciences, West Virginia University, Morgantown, WV, United States
| | - R Chris Skinner
- Food Systems Research Center, College of Agriculture and Life Sciences, University of Vermont Burlington, VT, United States
| | - Ayad Alawadi
- Division of Animal and Nutritional Sciences, West Virginia University, Morgantown, WV, United States
| | - Eloisa Vendemiatti
- Division of Plant and Soil Sciences, West Virginia University, Morgantown, WV, United States
| | - David J Laub
- Department of Biology, West Virginia University, Morgantown, WV, United States
| | - Casey Showman
- Division of Animal and Nutritional Sciences, West Virginia University, Morgantown, WV, United States
| | - Kristen Matak
- Division of Animal and Nutritional Sciences, West Virginia University, Morgantown, WV, United States
| | - Janet C Tou
- Division of Animal and Nutritional Sciences, West Virginia University, Morgantown, WV, United States.
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24
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Du Z, Wang Y, Li F, Sun X, Du Y, Li L, Yu H, Hu C, Sun H, Gao X, Han L, Zhang Z, Xing J, Wang L, Li J, Qin Y. Targeting Lysophosphatidic Acid Ameliorates Dyslipidemia in Familial Hypercholesterolemia. RESEARCH (WASHINGTON, D.C.) 2023; 8:0629. [PMID: 40018730 PMCID: PMC11865365 DOI: 10.34133/research.0629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 02/07/2025] [Accepted: 02/08/2025] [Indexed: 03/01/2025]
Abstract
Familial hypercholesterolemia (FH) is a lipoprotein disorder characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) and an increased risk of premature atherosclerotic cardiovascular disease. Recent evidences have shown that several glycerophospholipid species were markedly altered in experimental FH animals and exhibited diverse bioactivities. Nevertheless, the glycerophospholipid profiles and their associated biological implications in human FH remain largely unknown. In this study, we sought to comprehensively delineate the glycerophospholipid phenotypes in human FH and to investigate the functional roles of key FH-altered glycerophospholipid molecules on cholesterol metabolism. Targeted analysis of 328 glycerophospholipid metabolites was used to profile the differentiated alterations in patients with homozygous FH (HoFH; n = 181), heterozygous FH (HeFH; n = 452), and non-FH hypercholesterolemia (n = 382). Our findings revealed that the glycerophospholipid phenotypes of FH and non-FH hypercholesterolemia were dominated by a spectrum of metabolites involved in the lysophosphatidic acid (LPA) metabolism. Among the LPA features, palmitoyl-LPA (16:0) showed significant association with the clinical levels of LDL-C and total cholesterol in HoFH and HeFH populations. Using functional metabolomic strategy and murine FH model, we demonstrated that supplementation with LPA 16:0 elevated the plasma levels of LDL and free/esterified cholesterol and exacerbated the atherosclerotic lesions. Conversely, inhibition of autotaxin-mediated LPA 16:0 production significantly ameliorated dyslipidemia. Mechanistically, we uncovered that LPA 16:0 could disrupt hepatic cholesterol homeostasis by impairing cholesterol excretion and inhibiting primary bile acid synthesis. In summary, our study offers novel insights into lipid metabolism in human FH and posits that targeting LPA metabolism may represent a promising therapeutic strategy for reducing cholesterol levels in the FH population.
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Affiliation(s)
- Zhiyong Du
- Beijing Anzhen Hospital,
Capital Medical University, National Clinical Research Center for Cardiovascular Diseases, Beijing 100029, China
- Beijing Institute of Heart Lung and Blood Vessel Disease, Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China
| | - Yu Wang
- Beijing Anzhen Hospital,
Capital Medical University, National Clinical Research Center for Cardiovascular Diseases, Beijing 100029, China
- Beijing Institute of Heart Lung and Blood Vessel Disease, Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China
| | - Fan Li
- Beijing Anzhen Hospital,
Capital Medical University, National Clinical Research Center for Cardiovascular Diseases, Beijing 100029, China
- Beijing Institute of Heart Lung and Blood Vessel Disease, Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China
| | - Xuechun Sun
- Beijing Anzhen Hospital,
Capital Medical University, National Clinical Research Center for Cardiovascular Diseases, Beijing 100029, China
- Beijing Institute of Heart Lung and Blood Vessel Disease, Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China
| | - Yunhui Du
- Beijing Anzhen Hospital,
Capital Medical University, National Clinical Research Center for Cardiovascular Diseases, Beijing 100029, China
- Beijing Institute of Heart Lung and Blood Vessel Disease, Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China
| | - Linyi Li
- Beijing Anzhen Hospital,
Capital Medical University, National Clinical Research Center for Cardiovascular Diseases, Beijing 100029, China
- Beijing Institute of Heart Lung and Blood Vessel Disease, Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China
| | - Huahui Yu
- Beijing Anzhen Hospital,
Capital Medical University, National Clinical Research Center for Cardiovascular Diseases, Beijing 100029, China
- Beijing Institute of Heart Lung and Blood Vessel Disease, Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China
| | - Chaowei Hu
- Beijing Anzhen Hospital,
Capital Medical University, National Clinical Research Center for Cardiovascular Diseases, Beijing 100029, China
- Beijing Institute of Heart Lung and Blood Vessel Disease, Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China
| | - Haili Sun
- Beijing Anzhen Hospital,
Capital Medical University, National Clinical Research Center for Cardiovascular Diseases, Beijing 100029, China
- Beijing Institute of Heart Lung and Blood Vessel Disease, Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China
| | - Xiaoqian Gao
- Beijing Anzhen Hospital,
Capital Medical University, National Clinical Research Center for Cardiovascular Diseases, Beijing 100029, China
- Beijing Institute of Heart Lung and Blood Vessel Disease, Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China
| | - Lijie Han
- Beijing Anzhen Hospital,
Capital Medical University, National Clinical Research Center for Cardiovascular Diseases, Beijing 100029, China
- Beijing Institute of Heart Lung and Blood Vessel Disease, Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China
| | - Zihan Zhang
- Beijing Anzhen Hospital,
Capital Medical University, National Clinical Research Center for Cardiovascular Diseases, Beijing 100029, China
- Beijing Institute of Heart Lung and Blood Vessel Disease, Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China
| | - Jingci Xing
- Beijing Anzhen Hospital,
Capital Medical University, National Clinical Research Center for Cardiovascular Diseases, Beijing 100029, China
- Beijing Institute of Heart Lung and Blood Vessel Disease, Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China
| | - Luya Wang
- Beijing Anzhen Hospital,
Capital Medical University, National Clinical Research Center for Cardiovascular Diseases, Beijing 100029, China
- Beijing Institute of Heart Lung and Blood Vessel Disease, Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China
| | - Jianping Li
- Department of Cardiology,
Peking University First Hospital, Beijing 100034, China
| | - Yanwen Qin
- Beijing Anzhen Hospital,
Capital Medical University, National Clinical Research Center for Cardiovascular Diseases, Beijing 100029, China
- Beijing Institute of Heart Lung and Blood Vessel Disease, Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China
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25
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ZHONG JIATENG, GUO JINGYU, ZHANG XINYU, FENG SHUANG, DI WENYU, WANG YANLING, ZHU HUIFANG. The remodeling roles of lipid metabolism in colorectal cancer cells and immune microenvironment. Oncol Res 2023; 30:231-242. [PMID: 37305350 PMCID: PMC10207963 DOI: 10.32604/or.2022.027900] [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: 11/20/2022] [Accepted: 01/18/2023] [Indexed: 02/05/2023] Open
Abstract
Lipid is a key component of plasma membrane, which plays an important role in the regulation of various cell biological behaviors, including cell proliferation, growth, differentiation and intracellular signal transduction. Studies have shown that abnormal lipid metabolism is involved in many malignant processes, including colorectal cancer (CRC). Lipid metabolism in CRC cells can be regulated not only by intracellular signals, but also by various components in the tumor microenvironment, including various cells, cytokines, DNA, RNA, and nutrients including lipids. In contrast, abnormal lipid metabolism provides energy and nutrition support for abnormal malignant growth and distal metastasis of CRC cells. In this review, we highlight the remodeling roles of lipid metabolism crosstalk between the CRC cells and the components of tumor microenvironment.
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Affiliation(s)
- JIATENG ZHONG
- Department of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, China
- Department of Pathology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453100, China
| | - JINGYU GUO
- Department of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, China
| | - XINYU ZHANG
- Department of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, China
| | - SHUANG FENG
- Department of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, China
| | - WENYU DI
- Department of Pathology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453100, China
| | - YANLING WANG
- Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China
| | - HUIFANG ZHU
- Department of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, China
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26
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Huang Y, Cui Z, Wei X, Wang J, Yao J, Cai C, Wang J. Nicotinamide supplementation alters plasma lipidomic profiles of peripartal dairy cows. Anim Sci J 2023; 94:e13857. [PMID: 37496108 DOI: 10.1111/asj.13857] [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: 09/07/2022] [Revised: 05/16/2023] [Accepted: 06/20/2023] [Indexed: 07/28/2023]
Abstract
Fatty liver syndrome, a common health problem in dairy cows, occurs during the transition from pregnancy to lactation. If the energy supplied to the cow's body cannot meet its needs, a negative energy balance ensues, and the direct response is fat mobilization. Nicotinamide (NAM) has been reported to reduce the nonesterified fatty acid concentration of postpartum plasma. To study the biochemical adaptations underlying this physiologic dysregulation, 12 dairy cows were sequentially assigned to a NAM (45 g/day) treatment or control group. Blood samples were collected on day (D) 1 and D21 relative to parturition. Changes to the plasma lipid metabolism of dairy cows in the two groups were compared using lipidomics. There were significant increases in plasma sphingomyelins d18:1/18:0, d18:1/23:0, d18:1/24:1, d18:1/24:0, and d18:0/24:0 in the NAM group on D1 relative to parturition. In addition, fatty acids 18:2, 18:1, 18:0, 16:1, and 16:0 were obviously decreased on D21 relative to calving. This research has provided insights into how NAM supplementation improves lipid metabolism in perinatal dairy cows.
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Affiliation(s)
- Yan Huang
- College of Veterinary Medicine, Northwest A&F University, Xianyang, China
| | - Zhijie Cui
- College of Animal Science and Technology, Northwest A&F University, Xianyang, China
| | - Xiaoshi Wei
- College of Animal Science and Technology, Northwest A&F University, Xianyang, China
- College of Animal Science and Technology, College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, China
| | - Jiayu Wang
- Lipidall Technologies Company Limited, Changzhou, China
| | - Junhu Yao
- College of Animal Science and Technology, Northwest A&F University, Xianyang, China
| | - Chuanjiang Cai
- College of Animal Science and Technology, Northwest A&F University, Xianyang, China
| | - Jianguo Wang
- College of Veterinary Medicine, Northwest A&F University, Xianyang, China
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27
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Maestri M, Santopaolo F, Pompili M, Gasbarrini A, Ponziani FR. Gut microbiota modulation in patients with non-alcoholic fatty liver disease: Effects of current treatments and future strategies. Front Nutr 2023; 10:1110536. [PMID: 36875849 PMCID: PMC9978194 DOI: 10.3389/fnut.2023.1110536] [Citation(s) in RCA: 39] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 01/16/2023] [Indexed: 02/18/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is frequently associated with metabolic disorders, being highly prevalent in obese and diabetic patients. Many concomitant factors that promote systemic and liver inflammation are involved in NAFLD pathogenesis, with a growing body of evidence highlighting the key role of the gut microbiota. Indeed, the gut-liver axis has a strong impact in the promotion of NAFLD and in the progression of the wide spectrum of its manifestations, claiming efforts to find effective strategies for gut microbiota modulation. Diet is among the most powerful tools; Western diet negatively affects intestinal permeability and the gut microbiota composition and function, selecting pathobionts, whereas Mediterranean diet fosters health-promoting bacteria, with a favorable impact on lipid and glucose metabolism and liver inflammation. Antibiotics and probiotics have been used to improve NAFLD features, with mixed results. More interestingly, medications used to treat NAFLD-associated comorbidities may also modulate the gut microbiota. Drugs for the treatment of type 2 diabetes mellitus (T2DM), such as metformin, glucagon-like peptide-1 (GLP-1) agonists, and sodium-glucose cotransporter (SGLT) inhibitors, are not only effective in the regulation of glucose homeostasis, but also in the reduction of liver fat content and inflammation, and they are associated with a shift in the gut microbiota composition towards a healthy phenotype. Even bariatric surgery significantly changes the gut microbiota, mostly due to the modification of the gastrointestinal anatomy, with a parallel improvement in histological features of NAFLD. Other options with promising effects in reprogramming the gut-liver axis, such as fecal microbial transplantation (FMT) and next-generation probiotics deserve further investigation for future inclusion in the therapeutic armamentarium of NAFLD.
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Affiliation(s)
- Marta Maestri
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Francesco Santopaolo
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Maurizio Pompili
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.,Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.,Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Francesca Romana Ponziani
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.,Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
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Pezzino S, Sofia M, Faletra G, Mazzone C, Litrico G, La Greca G, Latteri S. Gut-Liver Axis and Non-Alcoholic Fatty Liver Disease: A Vicious Circle of Dysfunctions Orchestrated by the Gut Microbiome. BIOLOGY 2022; 11:1622. [PMID: 36358323 PMCID: PMC9687983 DOI: 10.3390/biology11111622] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Revised: 11/03/2022] [Accepted: 11/04/2022] [Indexed: 09/24/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a prevalent, multifactorial, and poorly understood liver disease with an increasing incidence worldwide. NAFLD is typically asymptomatic and coupled with other symptoms of metabolic syndrome. The prevalence of NAFLD is rising in tandem with the prevalence of obesity. In the Western hemisphere, NAFLD is one of the most prevalent causes of liver disease and liver transplantation. Recent research suggests that gut microbiome dysbiosis may play a significant role in the pathogenesis of NAFLD by dysregulating the gut-liver axis. The so-called "gut-liver axis" refers to the communication and feedback loop between the digestive system and the liver. Several pathological mechanisms characterized the alteration of the gut-liver axis, such as the impairment of the gut barrier and the increase of the intestinal permeability which result in endotoxemia and inflammation, and changes in bile acid profiles and metabolite levels produced by the gut microbiome. This review will explore the role of gut-liver axis disruption, mediated by gut microbiome dysbiosis, on NAFLD development.
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Affiliation(s)
| | | | | | | | | | | | - Saverio Latteri
- Department of Surgical Sciences and Advanced Technologies “G. F. Ingrassia”, Cannizzaro Hospital, University of Catania, 95126 Catania, Italy
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Xu R, Pan J, Zhou W, Ji G, Dang Y. Recent advances in lean NAFLD. Biomed Pharmacother 2022; 153:113331. [PMID: 35779422 DOI: 10.1016/j.biopha.2022.113331] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Revised: 06/20/2022] [Accepted: 06/22/2022] [Indexed: 02/09/2023] Open
Abstract
As the predominant type of chronic liver disease, the growing prevalence of nonalcoholic fatty liver disease (NAFLD) has become a concern worldwide. Although obesity plays the most pivotal role in NAFLD, approximately 10-20% of individuals with NAFLD who are not overweight or obese (BMI < 25 kg/m2, or BMI < 23 kg/m2 in Asians) have "lean NAFLD." Lean individuals with NAFLD have a lower prevalence of diabetes, hypertension, hypertriglyceridemia, central obesity, and metabolic syndrome than nonlean individuals with NAFLD, but higher fibrosis scores and rates of cardiovascular morbidity and all-cause mortality in advanced stages. The pathophysiological mechanisms of lean NAFLD remain poorly understood. Studies have shown that lean NAFLD is more correlated with factors such as environmental, genetic susceptibility, and epigenetic regulation. This review will examine the way in which the research progress and characteristic of lean NAFLD, and explore the function of epigenetic modification to provide the basis for the clinical treatment and diagnosis of lean NAFLD.
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Affiliation(s)
- Ruohui Xu
- Institute of Digestive Diseases, Longhua Hospital, China-Canada Center of Research for Digestive Diseases (ccCRDD), Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Jiashu Pan
- Institute of Digestive Diseases, Longhua Hospital, China-Canada Center of Research for Digestive Diseases (ccCRDD), Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; Department of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Wenjun Zhou
- Institute of Digestive Diseases, Longhua Hospital, China-Canada Center of Research for Digestive Diseases (ccCRDD), Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Guang Ji
- Institute of Digestive Diseases, Longhua Hospital, China-Canada Center of Research for Digestive Diseases (ccCRDD), Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
| | - Yanqi Dang
- Institute of Digestive Diseases, Longhua Hospital, China-Canada Center of Research for Digestive Diseases (ccCRDD), Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
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Vishnubhotla RV, Wood PL, Verma A, Cebak JE, Hariri S, Mudigonda M, Alankar S, Maturi R, Orui H, Subramaniam B, Palwale D, Renschler J, Sadhasivam S. Advanced Meditation and Vegan Diet Increased Acylglycines and Reduced Lipids Associated with Improved Health: A Prospective Longitudinal Study. JOURNAL OF INTEGRATIVE AND COMPLEMENTARY MEDICINE 2022; 28:674-682. [PMID: 35532984 DOI: 10.1089/jicm.2022.0480] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Introduction: Samyama is an Isha Yoga 8-day residential meditation/yoga retreat combined with 60 days of preparation with vegan diet. We showed earlier Samyama retreat was associated with lower systemic inflammation and favorable lipid profiles along with other physical and mental health benefits. There is no mechanistic study on the impact of an advanced meditative process on multiple blood lipids and their implications on meditation-related improved physical and mental wellbeing. Methods: Sixty-four Samyama participants on vegan diet had blood sampled immediately before and immediately after the 8-day retreat for lipidomic analysis. The complex plasma lipidome was characterized using high-resolution mass spectrometric analysis and tandem mass spectrometry. Results: Pre- and post-Samyama blood samples of 64 Samyama participants were analyzed. Acylglycines (acetyl, propionyl, butyryl, and valeryl) were increased in the plasma post-Samyama compared with pre-Samyama (p < 0.001). Levels of glycerophosphocholines, glycerophosphoethanolamines, di-unsaturated ethanolamine plasmalogens, cholesterol esters, acylcarnitines, and acylgylcerines (triacylglycerols and diacylglycerols) decreased after the Samyama meditation. Plasma levels of glycerophosphoserines or glycerophosphoinositols were unchanged. Conclusion: An 8-day advanced meditation retreat resulted in increased acylglycines, an endocannabinoid-like fatty acid amide associated with increased cellular anandamide levels, anti-inflammation, analgesia, and vascular relaxation. Other serum lipid levels, including some that are associated with increased risk of atherosclerosis, were reduced following the Samyama program. ClinicalTrials.gov Registration: Identifier: NCT04366544.
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Affiliation(s)
- Ramana V Vishnubhotla
- Department of Radiology, Indiana University School of Medicine, Indianpolis, IN, USA
| | - Paul L Wood
- Metabolomics Unit, College of Veterinary Medicine, Lincoln Memorial University, Harrogate, TN, USA
| | - Ashutosh Verma
- Metabolomics Unit, College of Veterinary Medicine, Lincoln Memorial University, Harrogate, TN, USA
| | - John E Cebak
- DeBusk College of Osteopathic Medicine, Lincoln Memorial University, Harrogate, TN, USA
| | - Sepideh Hariri
- Sadhguru Center for a Conscious Planet, Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boson, MA, USA
| | - Mayur Mudigonda
- Redwood Center for Theoretical Neuroscience, University of California, Berkeley, CA, USA
| | - Suresh Alankar
- Vascular Surgery, University of Louisville, Louisville, KY, USA
| | - Raj Maturi
- Department of Ophthalmology, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Hibiki Orui
- Sadhguru Center for a Conscious Planet, Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boson, MA, USA
| | - Balachundhar Subramaniam
- Sadhguru Center for a Conscious Planet, Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boson, MA, USA
| | - Dhanashri Palwale
- Department of Anesthesia, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Janelle Renschler
- Department of Anesthesia, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Senthilkumar Sadhasivam
- Department of Anesthesia, Indiana University School of Medicine, Indianapolis, IN, USA
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
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Overexpression of LPCAT1 enhances endometrial cancer stemness and metastasis by changing lipid components and activating the TGF/β-Smad2/3 signaling pathway. Acta Biochim Biophys Sin (Shanghai) 2022; 54:904-916. [PMID: 35880567 PMCID: PMC9827807 DOI: 10.3724/abbs.2022076] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
The incidence of endometrial cancer (EC) increases annually and tends to occur in younger women. A particularly important relationship exists between EC and metabolic disorders. As one of the most important components of lipid metabolism, phospholipids play an indispensable role in metabolic balance. LPCAT1 is a key enzyme regulating phospholipid metabolism. In this study, we perform further investigations to seek mechanistic insight of LPCAT1 in EC. Our results demonstrate that silencing of LPCAT1 inhibits the growth of endometrial cancer, while overexpression of LPCAT1 results in enhanced stemness and metastasis in endometrial cancer cell lines. Meanwhile, the contents of various phospholipids including phosphatidylethanolamine (PE), phosphatidylcholine (PC), and triglyceride (TG) change significantly after overexpression of LPCAT1. In addition, through RNA-sequencing and western blot analysis, we observe that the TGF-β/Smad2/3 signaling pathway is of great importance in the tumor-promoting function of LPCAT1. LPCAT1 promotes the expressions of stem cell-related transcription factors and epithelial-mesenchymal transition (EMT) related proteins through the TGF-β/Smad2/3 signaling pathway. Moreover, we find that TSI-01, which can inhibit the activity of LPCAT1, is able to restrain the proliferation of EC cell lines and promote cell apoptosis. Collectively, we demonstrate that LPCAT1 enhances the stemness and metastasis of EC by activating the TGF-β/Smad2/3 signaling pathway and that TSI-01 may have potential use for the treatment of EC.
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Furse S, Virtue S, Snowden SG, Vidal-Puig A, Stevenson PC, Chiarugi D, Koulman A. Dietary PUFAs drive diverse system-level changes in lipid metabolism. Mol Metab 2022; 59:101457. [PMID: 35150907 PMCID: PMC8894240 DOI: 10.1016/j.molmet.2022.101457] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 02/03/2022] [Accepted: 02/04/2022] [Indexed: 11/23/2022] Open
Abstract
OBJECTIVE Polyunsaturated fatty acid (PUFA) supplements have been trialled as a treatment for a number of conditions and produced a variety of results. This variety is ascribed to the supplements, that often comprise a mixture of fatty acids, and to different effects in different organs. In this study, we tested the hypothesis that the supplementation of individual PUFAs has system-level effects that are dependent on the molecular structure of the PUFA. METHODS We undertook a network analysis using Lipid Traffic Analysis to identify both local and system-level changes in lipid metabolism using publicly available lipidomics data from a mouse model of supplementation with FA(20:4n-6), FA(20:5n-3), and FA(22:6n-3); arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid, respectively. Lipid Traffic Analysis is a new computational/bioinformatics tool that uses the spatial distribution of lipids to pinpoint changes or differences in control of metabolism, thereby suggesting mechanistic reasons for differences in observed lipid metabolism. RESULTS There was strong evidence for changes to lipid metabolism driven by and dependent on the structure of the supplemented PUFA. Phosphatidylcholine and triglycerides showed a change in the variety more than the total number of variables, whereas phosphatidylethanolamine and phosphatidylinositol showed considerable change in both which variables and the number of them, in a highly PUFA-dependent manner. There was also evidence for changes to the endogenous biosynthesis of fatty acids and to both the elongation and desaturation of fatty acids. CONCLUSIONS These results show that the full biological impact of PUFA supplementation is far wider than any single-organ effect and implies that supplementation and dosing with PUFAs require a system-level assessment.
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Affiliation(s)
- Samuel Furse
- Core Metabolomics and Lipidomics Laboratory, Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Addenbrooke's Treatment Centre, Keith Day Road Cambridge, CB2 0QQ, UK; Wellcome-MRC Institute of Metabolic Science and Medical Research Council Metabolic Diseases Unit, University of Cambridge, Addenbrooke's Treatment Centre, Keith Day Road Cambridge, CB2 0QQ, UK; Royal Botanic Gardens, Kew, Kew Green, Richmond, Surrey, TW9 3AE, UK.
| | - Samuel Virtue
- Wellcome-MRC Institute of Metabolic Science and Medical Research Council Metabolic Diseases Unit, University of Cambridge, Addenbrooke's Treatment Centre, Keith Day Road Cambridge, CB2 0QQ, UK
| | - Stuart G Snowden
- Biology Department, Royal Holloway College, University of London, UK; Centro de Investigacion Principe Felipe, 46012 Valencia, Spain
| | - Antonio Vidal-Puig
- Wellcome-MRC Institute of Metabolic Science and Medical Research Council Metabolic Diseases Unit, University of Cambridge, Addenbrooke's Treatment Centre, Keith Day Road Cambridge, CB2 0QQ, UK
| | - Philip C Stevenson
- Royal Botanic Gardens, Kew, Kew Green, Richmond, Surrey, TW9 3AE, UK; Natural Resources Institute, University of Greenwich, Chatham, Kent ME4 4TB, UK
| | - Davide Chiarugi
- Bioinformatics and Biostatistics Core, Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Addenbrooke's Treatment Centre, Keith Day Road Cambridge, CB2 0QQ, UK
| | - Albert Koulman
- Core Metabolomics and Lipidomics Laboratory, Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Addenbrooke's Treatment Centre, Keith Day Road Cambridge, CB2 0QQ, UK; Wellcome-MRC Institute of Metabolic Science and Medical Research Council Metabolic Diseases Unit, University of Cambridge, Addenbrooke's Treatment Centre, Keith Day Road Cambridge, CB2 0QQ, UK.
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Rivas Serna IM, Sitina M, Stokin GB, Medina-Inojosa JR, Lopez-Jimenez F, Gonzalez-Rivas JP, Vinciguerra M. Lipidomic Profiling Identifies Signatures of Poor Cardiovascular Health. Metabolites 2021; 11:metabo11110747. [PMID: 34822405 PMCID: PMC8624456 DOI: 10.3390/metabo11110747] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Revised: 10/26/2021] [Accepted: 10/27/2021] [Indexed: 12/31/2022] Open
Abstract
Ideal cardiovascular health (CVH) is defined for the presence of ideal behavioral and health metrics known to prevent cardiovascular disease (CVD). The association of circulatory phospho- and sphingo-lipids to primary reduction in cardiovascular risk is unclear. Our aim was to determine the association of CVH metrics with the circulating lipid profile of a population-based cohort. Serum sphingolipid and phospholipid species were extracted from 461 patients of the randomly selected prospective Kardiovize study based on Brno, Czech Republic. Lipids species were measured by a hyphenated mass spectrometry technique, and were associated with poor CVH scores, as defined by the American Heart Association. Phosphatidylcholine (PC), phosphatidylethanolamine (PE), lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE) species were significantly lower in ideal and intermediate scores of health dietary metric, blood pressure, total cholesterol and blood fasting glucose compared to poor scores. Current smokers presented higher levels of PC, PE and LPE individual species compared to non-smokers. Ceramide (Cer) d18:1/14:0 was altered in poor blood pressure, total cholesterol and fasting blood glucose metrics. Poor cardiovascular health metric is associated with a specific phospho- and sphingolipid pattern. Circulatory lipid profiling is a potential biomarker to refine cardiovascular health status in primary prevention strategies.
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Affiliation(s)
- Irma Magaly Rivas Serna
- International Clinical Research Center (ICRC), St Anne’s University Hospital, 53, 656 91 Brno, Czech Republic; (I.M.R.S.); (M.S.); (G.B.S.); (J.P.G.-R.)
| | - Michal Sitina
- International Clinical Research Center (ICRC), St Anne’s University Hospital, 53, 656 91 Brno, Czech Republic; (I.M.R.S.); (M.S.); (G.B.S.); (J.P.G.-R.)
| | - Gorazd B. Stokin
- International Clinical Research Center (ICRC), St Anne’s University Hospital, 53, 656 91 Brno, Czech Republic; (I.M.R.S.); (M.S.); (G.B.S.); (J.P.G.-R.)
| | - Jose R. Medina-Inojosa
- Division of Preventive Cardiology, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN 55902, USA; (J.R.M.-I.); (F.L.-J.)
- Marriot Heart Disease Research Program, Rochester, MN 55902, USA
| | - Francisco Lopez-Jimenez
- Division of Preventive Cardiology, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN 55902, USA; (J.R.M.-I.); (F.L.-J.)
| | - Juan P. Gonzalez-Rivas
- International Clinical Research Center (ICRC), St Anne’s University Hospital, 53, 656 91 Brno, Czech Republic; (I.M.R.S.); (M.S.); (G.B.S.); (J.P.G.-R.)
- Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
| | - Manlio Vinciguerra
- International Clinical Research Center (ICRC), St Anne’s University Hospital, 53, 656 91 Brno, Czech Republic; (I.M.R.S.); (M.S.); (G.B.S.); (J.P.G.-R.)
- Correspondence:
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Goh YQ, Cheam G, Wang Y. Understanding Choline Bioavailability and Utilization: First Step Toward Personalizing Choline Nutrition. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2021; 69:10774-10789. [PMID: 34392687 DOI: 10.1021/acs.jafc.1c03077] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Choline is an essential macronutrient involved in neurotransmitter synthesis, cell-membrane signaling, lipid transport, and methyl-group metabolism. Nevertheless, the vast majority are not meeting the recommended intake requirement. Choline deficiency is linked to nonalcoholic fatty liver disease, skeletal muscle atrophy, and neurodegenerative diseases. The conversion of dietary choline to trimethylamine by gut microbiota is known for its association with atherosclerosis and may contribute to choline deficiency. Choline-utilizing bacteria constitutes less than 1% of the gut community and is modulated by lifestyle interventions such as dietary patterns, antibiotics, and probiotics. In addition, choline utilization is also affected by genetic factors, further complicating the impact of choline on health. This review overviews the complex interplay between dietary intakes of choline, gut microbiota and genetic factors, and the subsequent impact on health. Understanding of gut microbiota metabolism of choline substrates and interindividual variability is warranted in the development of personalized choline nutrition.
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Affiliation(s)
- Ying Qi Goh
- Singapore Phenome Center, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 636921
| | - Guoxiang Cheam
- School of Biological Sciences, Nanyang Technological University, Singapore 639798
| | - Yulan Wang
- Singapore Phenome Center, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 636921
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Perspectives on Mitochondria-ER and Mitochondria-Lipid Droplet Contact in Hepatocytes and Hepatic Lipid Metabolism. Cells 2021; 10:cells10092273. [PMID: 34571924 PMCID: PMC8472694 DOI: 10.3390/cells10092273] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 08/27/2021] [Accepted: 08/31/2021] [Indexed: 12/11/2022] Open
Abstract
Emerging evidence suggests that mitochondrion–endoplasmic reticulum (ER) and mitochondrion–lipid droplet (LD) contact sites are critical in regulating lipid metabolism in cells. It is well established that intracellular organelles communicate with each other continuously through membrane contact sites to maintain organelle function and cellular homeostasis. The accumulation of LDs in hepatocytes is an early indicator of non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD), which may indicate a breakdown in proper inter-organelle communication. In this review, we discuss previous findings in mitochondrion–ER and mitochondrion–LD contact, focusing on their roles in lipid metabolism in hepatocytes. We also present evidence of a unique mitochondrion–LD contact structure in hepatocytes under various physiological and pathological conditions and propose a working hypothesis to speculate about the role of these structures in regulating the functions of mitochondria and LDs and their implications in NAFLD and ALD.
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[¹¹C] choline as a potential PET/CT biomarker of liver cirrhosis: A prospective pilot study. Dig Liver Dis 2021; 53:753-759. [PMID: 33272861 DOI: 10.1016/j.dld.2020.11.013] [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: 08/30/2020] [Revised: 11/08/2020] [Accepted: 11/09/2020] [Indexed: 12/11/2022]
Abstract
AIM OF THE STUDY To compare [¹¹C] choline PET/CT findings between patients with cirrhosis and normal liver controls. METHODS Included 11 patients with cirrhosis and 14 controls. All underwent a dynamic [11C] choline PET/CT. The maximal standard uptake values (SUVmax), the area under the curve (AUC) and kinetic parameters (K1 and K2), clinical and laboratory data, were compared between groups. RESULTS Patients mean age was 68.4 ± 10.7 and controls, 69.7 ± 7.3 years. Mean SUVmax was higher in patients than controls (right lobe, 10.06 ± 12 vs. 6.3 ± 1.6, P = 0.011; left lobe, 8.6 ± 11.6 vs. 5.4 ± 0.9, P = 0.024; spleen 17.99 ± 27.8 vs. 13.4 ± 2.6, P = 0.027; kidney, 35.9 ± 59.5 vs. 19.3 ± 4.8, P = 0.025) and also AUC values (right lobe, 13,538 ± 20,020 vs. 8427.3 ± 1557.9, P = 0.026; left lobe 12,304 ± 18,871 vs. 6878.9 ± 1294.3, P = 0.024; spleen, 12,875 ± 17,930 vs. 8263.9 ± 1279.2, P = 0.023; kidney, 24,623 ± 36,025 vs. 13,667 ± 3873.9, P = 0.032). No difference in kinetic parameters was found. No correlations between severity of clinical signs and imaging-derived parametric data were found among patients with cirrhosis. CONCLUSIONS [11C] choline PET/CT may serve as a noninvasive biomarker for patients with cirrhosis.
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Zhou L, Lu R, Huang C, Lin D. Taurine Protects C2C12 Myoblasts From Impaired Cell Proliferation and Myotube Differentiation Under Cisplatin-Induced ROS Exposure. Front Mol Biosci 2021; 8:685362. [PMID: 34124164 PMCID: PMC8189557 DOI: 10.3389/fmolb.2021.685362] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 04/29/2021] [Indexed: 12/21/2022] Open
Abstract
In cancer patients, chemotherapeutic medication induces aberrant ROS (reactive oxygen species) accumulation in skeletal muscles, resulting in myofiber degradation, muscle weakness, and even cachexia, which further leads to poor therapeutic outcomes. Acting as an antioxidant, taurine is extensively used to accelerate postexercise muscle recovery in athletes. The antioxidant effects of taurine have been shown in mature myotubes and myofibers but not yet in myoblasts, the myotube precursor. The proliferation and differentiation ability of myoblasts play a very important role in myofiber repair and regeneration, which is usually impaired during chemotherapeutics in cancer patients as well. Here, we explored the effects of taurine supplementation on C2C12 myoblasts exposed to cisplatin-induced ROS. We found that cisplatin treatment led to dramatically decreased cell viability; accumulated ROS level; down-regulated expressions of MyoD1 (myoblast determination protein 1), myogenin, and MHC (myosin heavy chain); and impaired myotube differentiation in myoblasts. Significantly, taurine supplementation protected myoblasts against cisplatin-induced cell viability decrease, promoted cellular ROS clearance, and, most importantly, preserved the expressions of MyoD1, myogenin, and MHC as well as myotube differentiation ability. We further conducted NMR-based metabolomic analysis to clarify the underlying molecular mechanisms. We identified 14 characteristic metabolites primarily responsible for the discrimination of metabolic profiles between cisplatin-treated cells and normal counterparts, including increased levels of BCAAs (branched-chain amino acids: leucine and isoleucine), alanine, glycine, threonine, glucose, ADP (adenosine diphosphate), phenylalanine, and PC (O-phosphocholine), and decreased levels of lysine, β-alanine, choline, GPC (sn-glycero-3-phosphocholine), and myo-inositol. Evidently, taurine supplementation partially reversed the changing trends of several metabolites (isoleucine, threonine, glycine, PC, β-alanine, lysine, and myo-inositol). Furthermore, taurine supplementation promoted the proliferation and myotube differentiation of myoblasts by alleviating cellular catabolism, facilitating GSH (reduced glutathione) biosynthesis, improving glucose utilization and TCA (tricarboxylic acid) cycle anaplerosis, and stabilizing cellular membranes. Our results demonstrated the protective effects of taurine on cisplatin-impaired myoblasts and elucidated the mechanistic rationale for the use of taurine to ameliorate muscle toxicity in clinical chemotherapy cancer patients.
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Affiliation(s)
- Lin Zhou
- Key Laboratory for Chemical Biology of Fujian Province, MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China
| | - Ruohan Lu
- Key Laboratory for Chemical Biology of Fujian Province, MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China
| | - Caihua Huang
- Research and Communication Center of Exercise and Health, Xiamen University of Technology, Xiamen, China
| | - Donghai Lin
- Key Laboratory for Chemical Biology of Fujian Province, MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China
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Metabolomics shows the Australian dingo has a unique plasma profile. Sci Rep 2021; 11:5245. [PMID: 33664285 PMCID: PMC7933249 DOI: 10.1038/s41598-021-84411-6] [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: 12/01/2020] [Accepted: 02/04/2021] [Indexed: 01/02/2023] Open
Abstract
Dingoes occupy a wide range of the Australian mainland and play a crucial role as an apex predator with a generalist omnivorous feeding behaviour. Dingoes are ecologically, phenotypically and behaviourally distinct from modern breed dogs and have not undergone artificial selection since their arrival in Australia. In contrast, humans have selected breed dogs for novel and desirable traits. First, we examine whether the distinct evolutionary histories of dingoes and domestic dogs has lead to differences in plasma metabolomes. We study metabolite composition differences between dingoes (n = 15) and two domestic dog breeds (Basenji n = 9 and German Shepherd Dog (GSD) n = 10). Liquid chromatography mass spectrometry, type II and type III ANOVA with post-hoc tests and adjustments for multiple comparisons were used for data evaluation. After accounting for within group variation, 62 significant metabolite differences were detected between dingoes and domestic dogs, with the majority of differences in protein (n = 14) and lipid metabolites (n = 12), mostly lower in dingoes. Most differences were observed between dingoes and domestic dogs and fewest between the domestic dog breeds. Next, we collect a second set of data to investigate variation between pure dingoes (n = 10) and dingo-dog hybrids (n = 10) as hybridisation is common in regional Australia. We detected no significant metabolite differences between dingoes and dingo-dog hybrids after Bonferroni correction. However, power analysis showed that increasing the sample size to 15 could result in differences in uridine 5′-diphosphogalactose (UDPgal) levels related to galactose metabolism. We suggest this may be linked to an increase in Amylase 2B copy number in hybrids. Our study illustrates that the dingo metabolome is significantly different from domestic dog breeds and hybridisation is likely to influence carbohydrate metabolism.
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Fousekis FS, Mitselos IV, Christodoulou DK. New insights into intestinal failure-associated liver disease in adults: A comprehensive review of the literature. Saudi J Gastroenterol 2021; 27:3-12. [PMID: 33642350 PMCID: PMC8083246 DOI: 10.4103/sjg.sjg_551_20] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Intestinal failure-associated liver disease (IFALD) remains one of the most common and serious complications of parenteral nutrition (PN), causing a wide spectrum of hepatic manifestations from steatosis and mild cholestasis to portal hypertension and end-stage liver failure. The prevalence of IFALD depends on the diagnostic criteria and ranges from 4.3% to 65%. Moreover, many factors are shown to contribute to its development, including nutrient deficiencies, toxicity of PN, infections, and alterations of bile acid metabolism and gut microbiota. Prevention and management of IFALD aim at ameliorating or eliminating the risk factors associated with IFALD. The use of PN formulations with a lower ratio omega-6-to-omega-3 polyunsaturated fatty acids, cycle PN, optimization of enteral stimulation and prevention and early treatment of infections constitute the main therapeutic targets. However, failure of improvement and severe IFALD with end-stage liver failure should be considered as the indications of intestinal transplantation. The aim of this review is to provide an update of the epidemiology, pathophysiology, and diagnosis of IFALD in the adult population as well as to present a clinical approach of the therapeutic strategies of IFALD and present novel therapeutic targets.
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Affiliation(s)
- Fotios S. Fousekis
- Department of Gastroenterology and Hepatology, School of Health Sciences, University Hospital of Ioannina, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - Ioannis V. Mitselos
- Department of Gastroenterology and Hepatology, School of Health Sciences, University Hospital of Ioannina, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - Dimitrios K. Christodoulou
- Department of Gastroenterology and Hepatology, School of Health Sciences, University Hospital of Ioannina, Faculty of Medicine, University of Ioannina, Ioannina, Greece,Address for correspondence: Prof. Dimitrios K. Christodoulou, Professor of Gastroenterology, Department of Gastroenterology and Hepatology, School of Health Sciences, University Hospital of Ioannina, Faculty of Medicine, University of Ioannina, POBox 1186, Ioannina 45110, Greece. E-mail:
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Mehmood A, Zhao L, Wang Y, Pan F, Hao S, Zhang H, Iftikhar A, Usman M. Dietary anthocyanins as potential natural modulators for the prevention and treatment of non-alcoholic fatty liver disease: A comprehensive review. Food Res Int 2021; 142:110180. [PMID: 33773656 DOI: 10.1016/j.foodres.2021.110180] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Revised: 01/18/2021] [Accepted: 01/24/2021] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) refers to a metabolic syndrome linked with type 2 diabetes mellitus, obesity, and cardiovascular diseases. It is characterized by the accumulation of triglycerides in the hepatocytes in the absence of alcohol consumption. The prevalence of NAFLD has abruptly increased worldwide, with no effective treatment yet available. Anthocyanins (ACNs) belong to the flavonoid subclass of polyphenols, are commonly present in various edible plants, and possess a broad array of health-promoting properties. ACNs have been shown to have strong potential to combat NAFLD. We critically assessed the literature regarding the pharmacological mechanisms and biopharmaceutical features of the action of ACNs on NAFLD in humans and animal models. We found that ACNs ameliorate NAFLD by improving lipid and glucose metabolism, increasing antioxidant and anti-inflammatory activities, and regulating gut microbiota dysbiosis. In conclusion, ACNs have potential to attenuate NAFLD. However, further mechanistic studies are required to confirm these beneficial impacts of ACNs on NAFLD.
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Affiliation(s)
- Arshad Mehmood
- Beijing Advance Innovation Center for Food Nutrition and Human Health, Beijing Engineering and Technology Research Center of Food Additives, School of Food and Health, Beijing Technology and Business University, Beijing 100048, China
| | - Lei Zhao
- Beijing Advance Innovation Center for Food Nutrition and Human Health, Beijing Engineering and Technology Research Center of Food Additives, School of Food and Health, Beijing Technology and Business University, Beijing 100048, China.
| | - Yong Wang
- Academy of National Food and Strategic Reserves Administration, Beijing 100037, China
| | - Fei Pan
- Beijing Advance Innovation Center for Food Nutrition and Human Health, Beijing Engineering and Technology Research Center of Food Additives, School of Food and Health, Beijing Technology and Business University, Beijing 100048, China
| | - Shuai Hao
- Beijing Advance Innovation Center for Food Nutrition and Human Health, Beijing Engineering and Technology Research Center of Food Additives, School of Food and Health, Beijing Technology and Business University, Beijing 100048, China
| | - Huimin Zhang
- Beijing Advance Innovation Center for Food Nutrition and Human Health, Beijing Engineering and Technology Research Center of Food Additives, School of Food and Health, Beijing Technology and Business University, Beijing 100048, China
| | - Asra Iftikhar
- Department of Pharmacy, Faculty of Pharmaceutical Sciences, The University of Faisalabad, Faisalabad 38000, Pakistan
| | - Muhammad Usman
- Beijing Advance Innovation Center for Food Nutrition and Human Health, Beijing Engineering and Technology Research Center of Food Additives, School of Food and Health, Beijing Technology and Business University, Beijing 100048, China
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Zhao X, Feng X, Zhao X, Jiang Y, Li X, Niu J, Meng X, Wu J, Xu G, Hou L, Wang Y. How to Screen and Prevent Metabolic Syndrome in Patients of PCOS Early: Implications From Metabolomics. Front Endocrinol (Lausanne) 2021; 12:659268. [PMID: 34149613 PMCID: PMC8207510 DOI: 10.3389/fendo.2021.659268] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 05/11/2021] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) is a complex reproductive endocrine disorder. And metabolic syndrome (MS) is an important bridge for PCOS patients to develop other diseases, such as diabetes and coronary heart disease. Our aim was to study the potential metabolic characteristics of PCOS-MS and identify sensitive biomarkers so as to provide targets for clinical screening, diagnosis, and treatment. METHODS In this study, 44 PCOS patients with MS, 34 PCOS patients without MS, and 32 healthy controls were studied. Plasma samples of subjects were tested by ultraperformance liquid chromatography (UPLC) system combined with LTQ-orbi-trap mass spectrometry. The changes of metabolic characteristics from PCOS to PCOS-MS were systematically analyzed. Correlations between differential metabolites and clinical characteristics of PCOS-MS were assessed. Differential metabolites with high correlation were further evaluated by the receiver operating characteristic (ROC) curve to identify their sensitivity as screening indicators. RESULTS There were significant differences in general characteristics, reproductive hormone, and metabolic parameters in the PCOS-MS group when compared with the PCOS group and healthy controls. We found 40 differential metabolites which were involved in 23 pathways when compared with the PCOS group. The metabolic network further reflected the metabolic environment, including the interaction between metabolic pathways, modules, enzymes, reactions, and metabolites. In the correlation analysis, there were 11 differential metabolites whose correlation coefficient with clinical parameters was greater than 0.4, which were expected to be taken as biomarkers for clinical diagnosis. Besides, these 11 differential metabolites were assessed by ROC, and the areas under curve (AUCs) were all greater than 0.7, with a good sensitivity. Furthermore, combinational metabolic biomarkers, such as glutamic acid + leucine + phenylalanine and carnitine C 4: 0 + carnitine C18:1 + carnitine C5:0 were expected to be sensitive combinational biomarkers in clinical practice. CONCLUSION Our study provides a new insight to understand the pathogenesis mechanism, and the discriminating metabolites may help screen high-risk of MS in patients with PCOS and provide sensitive biomarkers for clinical diagnosis.
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Affiliation(s)
- Xiaoxuan Zhao
- Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Xiaoling Feng
- Department of Gynecology, the First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
| | - Xinjie Zhao
- Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
| | - Yuepeng Jiang
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xianna Li
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Jingyun Niu
- Centre for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xiaoyu Meng
- Department of Gynecology, the First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
| | - Jing Wu
- Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Guowang Xu
- Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
| | - Lihui Hou
- Department of Gynecology, the First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
- *Correspondence: Ying Wang, ; Lihui Hou,
| | - Ying Wang
- Department of Gynecology, the First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
- *Correspondence: Ying Wang, ; Lihui Hou,
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da Silva MT, Mujica-Coopman MF, Figueiredo ACC, Hampel D, Vieira LS, Farias DR, Shahab-Ferdows S, Allen LH, Brito A, Lamers Y, Kac G, S Vaz J. Maternal plasma folate concentration is positively associated with serum total cholesterol and low-density lipoprotein across the three trimesters of pregnancy. Sci Rep 2020; 10:20141. [PMID: 33214613 PMCID: PMC7677547 DOI: 10.1038/s41598-020-77231-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Accepted: 11/09/2020] [Indexed: 12/17/2022] Open
Abstract
Increased first-trimester low-density lipoprotein (LDL-C) concentration has been associated with adverse pregnancy outcomes, such as gestational diabetes. The B vitamins folate, B-6, and total B-12 are key for the methyl group-dependent endogenous synthesis of phosphatidylcholine, which is needed for lipoprotein synthesis, e.g., very low-density lipoprotein (VLDL), the precursor of circulating LDL-C. Maternal B-vitamin concentration usually declines across trimesters. Whether changes in maternal B-vitamin concentrations are associated with total cholesterol (TC), triglycerides (TG), and lipoprotein concentrations is unknown. Therefore, we explored the association between plasma folate, vitamin B-6 in the form of pyridoxal 5′-phosphate (PLP), and total B-12 with serum TC, LDL-C, HDL-C, and TG concentrations across trimesters. This secondary analysis used data of a prospective pregnancy cohort study included apparently healthy adult women (n = 179) from Rio de Janeiro, Brazil. The biomarkers were measured in fasting blood samples collected at 5–13, 20–26, and 30–36 weeks of gestation. The associations between B vitamins and lipid concentrations across trimesters were explored using linear mixed-effect models. Among B vitamins, only plasma folate was positively associated with TC (β = 0.244, 95% CI 0.034–0.454) and LDL-C (β = 0.193, 95% CI 0.028–0.357) concentrations. The positive relationship of maternal folate and TC and LDL-C concentrations may indicate the importance of folate as a methyl donor for lipoprotein synthesis during pregnancy.
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Affiliation(s)
- Manoela T da Silva
- Graduate Program in Food and Nutrition, Faculty of Nutrition, Universidade Federal de Pelotas, Rua Gomes Carneiro, 1, Pelotas, RS, 96010-610, Brazil
| | - Maria F Mujica-Coopman
- Food, Nutrition and Health Program, Faculty of Land and Food Systems, The University of British Columbia, Vancouver, BC, Canada
| | - Amanda C C Figueiredo
- Nutritional Epidemiology Observatory, Josué de Castro Nutrition Institute, Department of Social and Applied Nutrition, Rio de Janeiro Federal University, Rio de Janeiro, Brazil
| | - Daniela Hampel
- USDA-ARS Western Human Nutrition Research Center, Department of Nutrition, University of California, Davis, CA, USA
| | - Luna S Vieira
- Graduate Program in Epidemiology, Department of Social Medicine, Federal University of Pelotas, Pelotas, Brazil
| | - Dayana R Farias
- Nutritional Epidemiology Observatory, Josué de Castro Nutrition Institute, Department of Social and Applied Nutrition, Rio de Janeiro Federal University, Rio de Janeiro, Brazil
| | - Setareh Shahab-Ferdows
- USDA-ARS Western Human Nutrition Research Center, Department of Nutrition, University of California, Davis, CA, USA
| | - Lindsay H Allen
- USDA-ARS Western Human Nutrition Research Center, Department of Nutrition, University of California, Davis, CA, USA
| | - Alex Brito
- Laboratory of Pharmacokinetics and Metabolomic Analysis, Institute of Translational Medicine and Biotechnology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.,Department of Population Health, Nutrition and Health Research Group, Luxembourg Institute of Health, Strassen, Luxembourg
| | - Yvonne Lamers
- Food, Nutrition and Health Program, Faculty of Land and Food Systems, The University of British Columbia, Vancouver, BC, Canada
| | - Gilberto Kac
- Nutritional Epidemiology Observatory, Josué de Castro Nutrition Institute, Department of Social and Applied Nutrition, Rio de Janeiro Federal University, Rio de Janeiro, Brazil
| | - Juliana S Vaz
- Graduate Program in Food and Nutrition, Faculty of Nutrition, Universidade Federal de Pelotas, Rua Gomes Carneiro, 1, Pelotas, RS, 96010-610, Brazil. .,Nutritional Epidemiology Observatory, Josué de Castro Nutrition Institute, Department of Social and Applied Nutrition, Rio de Janeiro Federal University, Rio de Janeiro, Brazil. .,Graduate Program in Epidemiology, Department of Social Medicine, Federal University of Pelotas, Pelotas, Brazil.
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Yu Z, Li D, Yin F, Zhao Q, Liu Z, Song L, Zhou D, Wang T. Lipid Profiles in By‐Products and Muscles of Three Shrimp Species (
Penaeus monodon
,
Penaeus vannamei
, and
Penaeus chinensis
). EUR J LIPID SCI TECH 2020. [DOI: 10.1002/ejlt.201900309] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Affiliation(s)
- Zhuo‐Liang Yu
- School of Food Science and Technology Dalian Polytechnic University Dalian 116034 P. R. China
| | - De‐Yang Li
- School of Food Science and Technology Dalian Polytechnic University Dalian 116034 P. R. China
| | - Fa‐Wen Yin
- School of Food Science and Technology Dalian Polytechnic University Dalian 116034 P. R. China
- National Engineering Research Center of Seafood Dalian 116034 P. R. China
| | - Qi Zhao
- School of Food Science and Technology Dalian Polytechnic University Dalian 116034 P. R. China
- National Engineering Research Center of Seafood Dalian 116034 P. R. China
| | - Zhong‐Yuan Liu
- School of Food Science and Technology Dalian Polytechnic University Dalian 116034 P. R. China
| | - Liang Song
- School of Food Science and Technology Dalian Polytechnic University Dalian 116034 P. R. China
- National Engineering Research Center of Seafood Dalian 116034 P. R. China
| | - Da‐Yong Zhou
- School of Food Science and Technology Dalian Polytechnic University Dalian 116034 P. R. China
- National Engineering Research Center of Seafood Dalian 116034 P. R. China
| | - Tong Wang
- Department of Food Science University of Tennessee Knoxville TN 37996 USA
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44
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Yang G, Jang JH, Kim SW, Han SH, Ma KH, Jang JK, Kang HC, Cho YY, Lee HS, Lee JY. Sweroside Prevents Non-Alcoholic Steatohepatitis by Suppressing Activation of the NLRP3 Inflammasome. Int J Mol Sci 2020; 21:ijms21082790. [PMID: 32316419 PMCID: PMC7216241 DOI: 10.3390/ijms21082790] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Accepted: 04/15/2020] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic steatohepatitis (NASH), a type of non-alcoholic fatty liver disease, is characterized as steatosis and inflammation in the liver. NLRP3 inflammasome activation is associated with NASH pathology. We hypothesized that suppressing the NLRP3 inflammasome could be effective in preventing NASH. We searched substances that could inhibit the activation of the NLRP3 inflammasome and identified sweroside as an NLRP3 inhibitor. We investigated whether sweroside can be applied to prevent the pathological symptoms associated with NASH in a methionine–choline-deficient (MCD) diet-induced NASH mouse model. The activation of the NLRP3 inflammasome was determined by detecting the production of caspase-1 and IL-1β from pro-caspase-1 and pro-IL-1β in primary mouse macrophages and mouse liver. In a NASH model, mice were fed an MCD diet for two weeks with daily intraperitoneal injections of sweroside. Sweroside effectively inhibited NLRP3 inflammasome activation in primary macrophages as shown by a decrease in IL-1β and caspase-1 production. In a MCD diet-induced NASH mouse model, intraperitoneal injection of sweroside significantly reduced serum aspartate transaminase and alanine transaminase levels, hepatic immune cell infiltration, hepatic triglyceride accumulation, and liver fibrosis. The improvement of NASH symptoms by sweroside was accompanied with its inhibitory effects on the hepatic NLRP3 inflammasome as hepatic IL-1β and caspase-1 were decreased. Furthermore, sweroside blocked de novo synthesis of mitochondrial DNA in the liver, contributing to suppression of the NLRP3 inflammasome. These results suggest that targeting the NLRP3 inflammasome with sweroside could be beneficially employed to improve NASH symptoms.
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Affiliation(s)
- Gabsik Yang
- BK21plus Team, College of Pharmacy, The Catholic University of Korea, Bucheon 14662, Korea; (G.Y.); (J.H.J.); (S.W.K.); (H.C.K.); (Y.-Y.C.); (H.S.L.)
- Department of Pharmacology, College of Korean Medicine, Woosuk University, Jeonbuk 55338, Korea
| | - Joo Hyeon Jang
- BK21plus Team, College of Pharmacy, The Catholic University of Korea, Bucheon 14662, Korea; (G.Y.); (J.H.J.); (S.W.K.); (H.C.K.); (Y.-Y.C.); (H.S.L.)
| | - Sung Wook Kim
- BK21plus Team, College of Pharmacy, The Catholic University of Korea, Bucheon 14662, Korea; (G.Y.); (J.H.J.); (S.W.K.); (H.C.K.); (Y.-Y.C.); (H.S.L.)
| | - Sin-Hee Han
- Department of Herbal Crop Research, National Institute of Horticultural & Herbal Science, Rural Development Administration, Eumsung 27709, Korea; (S.-H.H.); (K.-H.M.); (J.-K.J.)
| | - Kyung-Ho Ma
- Department of Herbal Crop Research, National Institute of Horticultural & Herbal Science, Rural Development Administration, Eumsung 27709, Korea; (S.-H.H.); (K.-H.M.); (J.-K.J.)
| | - Jae-Ki Jang
- Department of Herbal Crop Research, National Institute of Horticultural & Herbal Science, Rural Development Administration, Eumsung 27709, Korea; (S.-H.H.); (K.-H.M.); (J.-K.J.)
| | - Han Chang Kang
- BK21plus Team, College of Pharmacy, The Catholic University of Korea, Bucheon 14662, Korea; (G.Y.); (J.H.J.); (S.W.K.); (H.C.K.); (Y.-Y.C.); (H.S.L.)
| | - Yong-Yeon Cho
- BK21plus Team, College of Pharmacy, The Catholic University of Korea, Bucheon 14662, Korea; (G.Y.); (J.H.J.); (S.W.K.); (H.C.K.); (Y.-Y.C.); (H.S.L.)
| | - Hye Suk Lee
- BK21plus Team, College of Pharmacy, The Catholic University of Korea, Bucheon 14662, Korea; (G.Y.); (J.H.J.); (S.W.K.); (H.C.K.); (Y.-Y.C.); (H.S.L.)
| | - Joo Young Lee
- BK21plus Team, College of Pharmacy, The Catholic University of Korea, Bucheon 14662, Korea; (G.Y.); (J.H.J.); (S.W.K.); (H.C.K.); (Y.-Y.C.); (H.S.L.)
- Correspondence: ; Tel.: +82-2-2164-4095; Fax: +82-2-2164-4059
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Talavera-Urquijo E, Beisani M, Balibrea JM, Alverdy JC. Is bariatric surgery resolving NAFLD via microbiota-mediated bile acid ratio reversal? A comprehensive review. Surg Obes Relat Dis 2020; 16:1361-1369. [PMID: 32336663 DOI: 10.1016/j.soard.2020.03.013] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2019] [Revised: 01/18/2020] [Accepted: 03/11/2020] [Indexed: 02/07/2023]
Abstract
Despite the fact that there is still insufficient evidence to consider non-alcoholic fatty liver disease (NAFLD) as an stand-alone indication for bariatric surgery, many clinical and histopathological beneficial effects on both NAFLD and non-alcoholic steatohepatitis (NASH) have been shown. Although weight loss seems to be the obvious mechanism, weight-loss independent factors are also believed to be involved. Among them, changes in gut microbiota and bile acids (BA) composition may be playing an unappreciated role in the improvement of NAFLD. In this review we examine the mechanisms and interdependence of the gut microbiota and BA, and their influence on NAFLD pathogenesis and its reversal following bariatric surgery. According to the currently available evidence, gut microbiota has a major influence on BA composition. In fact, both BA and microbiome disturbances (dysbiosis) play a role in the etiopathogenesis of NAFLD and might be potential therapeutic targets. In addition, bariatric surgery can modify the intraluminal ileal environment in a way that causes significant repopulation of the gut microbiota and a reversal of the plasma primary/secondary BA ratio, which, in turn, induces weigh-independent metabolic improvements.
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Affiliation(s)
- Eider Talavera-Urquijo
- Department of General & Digestive Surgery, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Marc Beisani
- Department of Surgery, Hospital del Mar, Barcelona, Spain
| | - José M Balibrea
- Department of Gastrointestinal Surgery, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain.
| | - John C Alverdy
- Department of Surgery University of Chicago, Pritzker School of Medicine, Chicago, Illinois
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Vakhrushev YM, Suchkova EV, Lukashevich AP. [Non - alcoholic fatty liver disease and enteral insufficiency: comorbidity of their development]. TERAPEVT ARKH 2019; 91:84-89. [PMID: 32598594 DOI: 10.26442/00403660.2019.12.000134] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Indexed: 01/10/2023]
Abstract
The article reflects current literature data on the epidemiology and risk factors of non - alcoholic fatty liver disease. An important aspect is the description of the modern views of combined lesions of the hepatobiliary tract and small intestine. Disorders of the intestinal microbiota play a special role in the development of non - alcoholic fatty liver disease. The value of enterohepatic circulation of bile acids in the development of intestinal and liver diseases was shown. It seems relevant to further study the comorbidity of the development of non - alcoholic fatty liver disease and enteropathy for the development of pathogenetically substantiated therapy.
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47
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Simoes IC, Janikiewicz J, Bauer J, Karkucinska-Wieckowska A, Kalinowski P, Dobrzyń A, Wolski A, Pronicki M, Zieniewicz K, Dobrzyń P, Krawczyk M, Zischka H, Wieckowski MR, Potes Y. Fat and Sugar-A Dangerous Duet. A Comparative Review on Metabolic Remodeling in Rodent Models of Nonalcoholic Fatty Liver Disease. Nutrients 2019; 11:2871. [PMID: 31771244 PMCID: PMC6950566 DOI: 10.3390/nu11122871] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Revised: 11/20/2019] [Accepted: 11/21/2019] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a common disease in Western society and ranges from steatosis to steatohepatitis to end-stage liver disease such as cirrhosis and hepatocellular carcinoma. The molecular mechanisms that are involved in the progression of steatosis to more severe liver damage in patients are not fully understood. A deeper investigation of NAFLD pathogenesis is possible due to the many different animal models developed recently. In this review, we present a comparative overview of the most common dietary NAFLD rodent models with respect to their metabolic phenotype and morphological manifestation. Moreover, we describe similarities and controversies concerning the effect of NAFLD-inducing diets on mitochondria as well as mitochondria-derived oxidative stress in the progression of NAFLD.
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Affiliation(s)
- Ines C.M. Simoes
- Nencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, Poland (J.J.); (A.D.); (P.D.); (Y.P.)
| | - Justyna Janikiewicz
- Nencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, Poland (J.J.); (A.D.); (P.D.); (Y.P.)
| | - Judith Bauer
- Institute of Toxicology and Environmental Hygiene, Technical University Munich, School of Medicine, Biedersteiner Strasse 29, D-80802 Munich, Germany; (J.B.); (H.Z.)
| | | | - Piotr Kalinowski
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, 02-091 Warsaw, Poland; (P.K.); (K.Z.)
| | - Agnieszka Dobrzyń
- Nencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, Poland (J.J.); (A.D.); (P.D.); (Y.P.)
| | - Andrzej Wolski
- Department of Interventional Radiology and Neuroradiology, Medical University of Lublin, 20-090 Lublin, Poland;
| | - Maciej Pronicki
- Department of Pathology, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland; (A.K.-W.); (M.P.)
| | - Krzysztof Zieniewicz
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, 02-091 Warsaw, Poland; (P.K.); (K.Z.)
| | - Paweł Dobrzyń
- Nencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, Poland (J.J.); (A.D.); (P.D.); (Y.P.)
| | - Marcin Krawczyk
- Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Centre for Preclinical Research, Medical University of Warsaw, 02-091 Warsaw, Poland;
- Department of Medicine II, Saarland University Medical Center, 66421 Homburg, Germany
| | - Hans Zischka
- Institute of Toxicology and Environmental Hygiene, Technical University Munich, School of Medicine, Biedersteiner Strasse 29, D-80802 Munich, Germany; (J.B.); (H.Z.)
- Institute of Molecular Toxicology and Pharmacology, Helmholtz Center Munich, German Research Center for Environmental Health, Ingolstaedter Landstrasse 1, D-85764 Neuherberg, Germany
| | - Mariusz R. Wieckowski
- Nencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, Poland (J.J.); (A.D.); (P.D.); (Y.P.)
| | - Yaiza Potes
- Nencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, Poland (J.J.); (A.D.); (P.D.); (Y.P.)
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Wolke C, Gürtler S, Peter D, Weingärtner J, Domanska G, Lendeckel U, Schild L. Vitamin B6 deficiency in new born rats affects hepatic cardiolipin composition and oxidative phosphorylation. Exp Biol Med (Maywood) 2019; 244:1619-1628. [PMID: 31752529 DOI: 10.1177/1535370219889880] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Vitamin B6 deficiency during pregnancy translates into a severe vitamin B6 deficiency (plasma levels decreased by 97%) in new-born rats. Further, hallmarks are increased (+89%) concentrations of homocysteine, gross changes in gene methylation and expression, and metabolic alterations including lipid metabolism. This study focuses on determining the effects of vitamin B6-deficiency on cardiolipin composition and oxidative phosphorylation in liver. For this purpose, hepatic cardiolipin composition was analyzed by means of LC/MS/MS, and mitochondrial oxygen consumption was determined by using a Clark-type electrode in a rat model of vitamin B6 deficiency. Liver mitochondria from new-born rats with pre-term vitamin B6 deficiency responded with substantial alterations in cardiolipin composition that include the following changes in the amounts of cardiolipin incorporated fatty acids: increase in C16, decrease in C18, decrease in saturated fatty acid, as well as increase in amount of oxidized cardiolipin species. These changes were accompanied by significantly decreased capacity of oxidative phosphorylation. In conclusion, vitamin B6 deficiency in new born rats induces massive alterations of cardiolipin composition and function of liver mitochondria. These findings support the importance of sufficient periconceptional supply of vitamin B6 to prevent vitamin B6 deficiency.Impact statementVitamin B6 (VitB6) is an active co-enzyme for more than 150 enzymes and is required for a great diversity of biosynthesis and metabolic reactions. There is an increased need for VitB6 during pregnancy and sufficient supply of VitB6 is crucial for the prevention of cleft palate and neural tube defects. We show that liver mitochondria from new-born rats with pre-term VitB6 deficiency respond with substantial alterations in cardiolipin (CL) composition and in the amount of oxidized CL species. These changes are associated with a decrease in the efficiency of oxidative phosphorylation. The results of this study support the significance of sufficient supply of VitB6 during pregnancy (and periconceptional) for diminishing the number of early abortions and minimizing malformation. The established link between VitB6 deficiency, CL composition, and mitochondrial respiration/energy production provides mechanistic insight as to how the VitB6 deficiency translates into the known pathophysiological and clinically relevant conditions.
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Affiliation(s)
- Carmen Wolke
- Institute of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, Greifswald D-17475, Germany
| | - Sarah Gürtler
- Institute of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, Greifswald D-17475, Germany
| | - Daniela Peter
- Department of Pathological Biochemistry, Otto-von-Guericke University Magdeburg, Magdeburg D-39120, Germany
| | - Jens Weingärtner
- Institute of Anatomy and Cell Biology, University Medicine Greifswald, Greifswald D-17489, Germany
| | - Grazyna Domanska
- Institute of Immunology, University Medicine Greifswald, Greifswald D-17475, Germany
| | - Uwe Lendeckel
- Institute of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, Greifswald D-17475, Germany
| | - Lorenz Schild
- Department of Pathological Biochemistry, Otto-von-Guericke University Magdeburg, Magdeburg D-39120, Germany
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Iruarrizaga-Lejarreta M, Arretxe E, Alonso C. Using metabolomics to develop precision medicine strategies to treat nonalcoholic steatohepatitis. EXPERT REVIEW OF PRECISION MEDICINE AND DRUG DEVELOPMENT 2019. [DOI: 10.1080/23808993.2019.1685379] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
| | - Enara Arretxe
- OWL Metabolomics, Parque Tecnológico de Bizkaia, Derio, Spain
| | - Cristina Alonso
- OWL Metabolomics, Parque Tecnológico de Bizkaia, Derio, Spain
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50
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Dong XF, Zhai QH, Tong JM. Dietary choline supplementation regulated lipid profiles of egg yolk, blood, and liver and improved hepatic redox status in laying hens. Poult Sci 2019; 98:3304-3312. [PMID: 30941414 DOI: 10.3382/ps/pez139] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Accepted: 03/08/2019] [Indexed: 12/21/2022] Open
Abstract
Five hundred and forty 19-wk-old HyLine Brown laying hens were randomly distributed to 6 dietary treatments and fed 1of 6 corn-soybean meal-based diets added into choline with 0, 425, 850, 1,700, 3,400, and 6,800 mg/kg to investigate effects of dietary choline supplementation on lipid profiles of egg yolk, serum and liver, and hepatic redox status of laying hens. Yolk weight and total lipid, triglyceride, cholesterol and phosphatidylcholine, serum triglyceride, cholesterol, apolipoprotein B 100 (apoB 100), and very low density lipoprotein (VLDL), and liver relative weight, total lipid, triglyceride and apoB 100 as well as hepatic total superoxide dismutase and glutathione peroxidase (GSH-Px) activities, total antioxidant capacity (T-AOC), and malondialdehyde (MDA) in laying hens at weeks 58 and 68 of age were determined. The differences (P < 0.001) were caused by choline treatments in yolk phosphatidylcholine (at 850 mg/kg or more choline), serum VLDL, and liver triglyceride (at 1,700 and 3,400 mg/kg choline) of birds, at weeks 58 and 68 of age, and yolk total lipids were elevated (P < 0.05) by supplemental choline at 3,400 mg/kg whereas liver total lipids were reduced (P < 0.05) by 1,700 and 3,400 mg/kg choline addition. Hens fed diets supplemented choline had higher (P = 0.005) liver GSH-Px activity (with 3,400 mg/kg choline) and greater (P = 0.014) T-AOC (with 1,700 mg/kg choline) than those fed diets with 0 and 425 mg/kg choline addition. Choline affected serum VLDL, liver total lipid, triglyceride and apoB 100 at weeks 58 and 68 of age and hepatic GSH-Px activity, T-AOC and MDA at week 68 of age quadratically (P < 0.05), whereas it influenced total lipid and phosphatidylcholine of egg yolk linearly (P < 0.05) and quadratically (P < 0.05). In conclusion, dietary choline supplementation elevated yolk total lipid and phosphatidylcholine and serum VLDL, reduced liver total lipid and triglyceride, and enhanced hepatic GSH-Px activity and T-AOC in laying hens.
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Affiliation(s)
- X F Dong
- Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Q H Zhai
- Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
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