ArticleHepatology research : the official journal of the Japan Society of Hepatology2011
Peroxisome proliferator-activated receptor agonist treatment of alcohol-induced hepatic insulin resistance.
Article in Hepatology research : the official journal of the Japan Society of Hepatology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 43 citations in OpenAlex.
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- Trigonella foenum-graecum water extract improves insulin sensitivity and stimulates PPAR and γ gene expression in high fructose-fed insulin-resistant rats.Advanced biomedical research · 2016Article
- Impact of Alcohol on Glycemic Control and Insulin Action.Biomolecules · 2015Review
- Insulin resistance in clinical and experimental alcoholic liver disease.Annals of the New York Academy of Sciences · 2015Review
- Therapeutic reversal of chronic alcohol-related steatohepatitis with the ceramide inhibitor myriocin.International journal of experimental pathology · 2014Article
- Zataria multiflora increases insulin sensitivity and PPARγ gene expression in high fructose fed insulin resistant rats.Iranian journal of basic medical sciences · 2014Article
- Absence of perilipin 2 prevents hepatic steatosis, glucose intolerance and ceramide accumulation in alcohol-fed mice.PloS one · 2014Article
- Ceramide inhibitor myriocin restores insulin/insulin growth factor signaling for liver remodeling in experimental alcohol-related steatohepatitis.Journal of gastroenterology and hepatology · 2013Article
- Temporal effects of ethanol consumption on energy homeostasis, hepatic steatosis, and insulin sensitivity in mice.Alcoholism, clinical and experimental research · 2013Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
aimChronic ethanol exposure impairs insulin signaling in the liver. Peroxisome-proliferator activated receptor (PPAR) agonists function as insulin sensitizers and are used to treat type 2 diabetes mellitus. We examined the therapeutic effectiveness of PPAR agonists in reducing alcoholic hepatitis and hepatic insulin resistance in a model of chronic ethanol feeding.
methodsAdult male Long Evans rats were pair fed with isocaloric liquid diets containing 0% (control) or 37% ethanol (caloric content; 9.2% v/v) for 8 weeks. After 3 weeks on the diets, the rats were treated with vehicle, or a PPAR-α, PPAR-δ or PPAR-γ agonist twice weekly by i.p. injection. Livers were harvested for histopathological, gene expression (reverse transcription polymerase chain reaction), protein (western and ELISA) and receptor binding studies.
resultsEthanol-fed rats developed steatohepatitis with disordered hepatic chord architecture, increased hepatocellular apoptosis, reduced binding to the insulin, insulin-like growth factor (IGF)-1 and IGF-2 receptors, and decreased expression of glyceraldehyde-3-phosphate dehydrogenase and aspartyl-(asparaginyl)-β-hydroxylase (mediating remodeling), which are regulated by insulin/IGF signaling. PPAR-α, PPAR-δ or PPAR-γ agonist treatments reduced the severity of ethanol-mediated liver injury, including hepatic architectural disarray and steatosis. In addition, PPAR-δ and PPAR-γ agonists reduced insulin/IGF resistance and increased insulin/IGF-responsive gene expression.
conclusionPPAR agonists may help reduce the severity of chronic ethanol-induced liver injury and insulin/IGF resistance, even in the context of continued high-level ethanol consumption.
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