ArticleAlcoholism, clinical and experimental research2013
Preservation of hepatocyte nuclear factor-4α contributes to the beneficial effect of dietary medium chain triglyceride on alcohol-induced hepatic lipid dyshomeostasis in rats.
Article in Alcoholism, clinical and experimental research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- Alcohol consumption may be a risk factor for cerebrovascular stenosis in acute ischemic stroke and transient ischemic attack.BMC neurology · 2024Article
- Current Insights Regarding Intestinal Failure-Associated Liver Disease (IFALD): A Narrative Review.Nutrients · 2023Review
- Chronic-binge ethanol feeding aggravates systemic dyslipidemia inFrontiers in endocrinology · 2023Article
- The Preliminary Results for Evaluating Cocoa Butter's Hepatoprotective Effects against Lipid Accumulation and Inflammation in Adult Male Rats Chronically Fed Ethanol.Bioengineering (Basel, Switzerland) · 2022Article
- Review
- Perspectives of lipid metabolism reprogramming in head and neck squamous cell carcinoma: An overview.Frontiers in oncology · 2022Review
- Impact of Parenteral Lipid Emulsion Components on Cholestatic Liver Disease in Neonates.Nutrients · 2021Review
- Alcohol effects on hepatic lipid metabolism.Journal of lipid research · 2020Review
- Effect of ethanol on lipid metabolism.Journal of hepatology · 2019Review
- Medium-Chain Triglycerides Attenuate Liver Injury in Lipopolysaccharide-Challenged Pigs by Inhibiting Necroptotic and Inflammatory Signaling Pathways.International journal of molecular sciences · 2018Article
- Effects of Fish Oil on Lipid Metabolism and Its Molecular Biological Regulators in Chronic Ethanol-Fed Rats.Nutrients · 2018Article
- Adipose-specific lipin1 overexpression in mice protects against alcohol-induced liver injury.Scientific reports · 2018Article
- Article
- Dietary Linoleic Acid and Its Oxidized Metabolites Exacerbate Liver Injury Caused by Ethanol via Induction of Hepatic Proinflammatory Response in Mice.The American journal of pathology · 2017Article
- Hepatic overproduction of 13-HODE due to ALOX15 upregulation contributes to alcohol-induced liver injury in mice.Scientific reports · 2017Article
- Dietary Fisetin Supplementation Protects Against Alcohol-Induced Liver Injury in Mice.Alcoholism, clinical and experimental research · 2016Article
- Aberrant post-translational protein modifications in the pathogenesis of alcohol-induced liver injury.World journal of gastroenterology · 2016Review
- Medium-chain triglyceride ameliorates insulin resistance and inflammation in high fat diet-induced obese mice.European journal of nutrition · 2016Article
- Alcoholic Liver Disease: Update on the Role of Dietary Fat.Biomolecules · 2016Review
- Thyrotropin and obesity: increased adipose triglyceride content through glycerol-3-phosphate acyltransferase 3.Scientific reports · 2015Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAlcohol consumption is a major cause of fatty liver, and dietary saturated fats have been shown to protect against alcoholic fatty liver. This study investigated the mechanisms of how dietary saturated fat may modulate alcohol-induced hepatic lipid dyshomeostasis.
methodsMale Sprague Dawley rats were pair-fed with 3 isocaloric liquid diets, control, alcohol, and medium chain triglyceride (MCT)/alcohol, respectively, for 8 weeks. The control and alcohol diets were based on the Lieber-DeCarli liquid diet formula with 30% total calories derived from corn oil (rich in unsaturated long chain fatty acids). The corn oil was replaced by MCT, which consists of exclusive saturated fatty acids, in the MCT/alcohol diet. HepG2 cell culture was conducted to test the effects of unsaturated fatty acids on hepatocyte nuclear factor-4α (HNF4α) and the role of HNF4α in regulating hepatocyte lipid homeostasis.
resultsAlcohol feeding caused significant lipid accumulation, which was attenuated by dietary MCT. The major effect of alcohol on hepatic gene expression is the up-regulation of CYP4A1, CD36, and GPAT3, and down-regulation of apolipoprotein B (ApoB). Dietary MCT further up-regulated CYP4A1 gene, normalized ApoB gene, and up-regulated MTTP and SCD1 genes. The protein level of HNF4α, a master transcription factor of the liver, was reduced by alcohol feeding, which was normalized by dietary MCT. Fatty acid profiling demonstrated that alcohol feeding dramatically increased hepatic unsaturated long chain fatty acyl species, particularly linoleic acid and oleic acid, which was attenuated by dietary MCT. Dietary MCT attenuated alcohol-reduced serum triglyceride level and modulated the fatty acid composition of the serum triglycerides. Cell culture study demonstrated polyunsaturated linoleic acid rather than monounsaturated oleic acid inactivated HNF4α in HepG2 cells. Knockdown of HNF4α caused lipid accumulation in HepG2 cells due to dysregulation of very low density lipoprotein secretion.
conclusionsResults suggest that dietary MCT prevents alcohol-induced hepatic lipid accumulation, at least partially, through reducing hepatic polyunsaturated long chain fatty acids and preserving HNF4α.
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