The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice
TLDR
Adiponectin was effective in ameliorating hepatomegaly, steatosis, and alanine aminotransferase abnormality associated with nonalcoholic obese, ob/ob mice and could suppress the hepatic production of TNF-alpha and plasma concentrations of this proinflammatory cytokine.Abstract:
Adiponectin has recently been shown to be a promising candidate for the treatment of obesity-associated metabolic syndromes. Replenishment of recombinant adiponectin in mice can decrease hyperglycemia, reverse insulin resistance, and cause sustained weight loss without affecting food intake. Here we report its potential roles in alcoholic and nonalcoholic fatty liver diseases in mice. Circulating concentrations of adiponectin decreased significantly following chronic consumption of high-fat ethanol-containing food. Delivery of recombinant adiponectin into these mice dramatically alleviated hepatomegaly and steatosis (fatty liver) and also significantly attenuated inflammation and the elevated levels of serum alanine aminotransferase. These therapeutic effects resulted partly from the ability of adiponectin to increase carnitine palmitoyltransferase I activity and enhance hepatic fatty acid oxidation, while it decreased the activities of two key enzymes involved in fatty acid synthesis, including acetyl-CoA carboxylase and fatty acid synthase. Furthermore, adiponectin treatment could suppress the hepatic production of TNF-alpha and plasma concentrations of this proinflammatory cytokine. Adiponectin was also effective in ameliorating hepatomegaly, steatosis, and alanine aminotransferase abnormality associated with nonalcoholic obese, ob/ob mice. These results demonstrate a novel mechanism of adiponectin action and suggest a potential clinical application of adiponectin and its agonists in the treatment of liver diseases.read more
Citations
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The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD)
TL;DR: The 'two-hit' hypothesis is now obsolete, as it is inadequate to explain the several molecular and metabolic changes that take place in NAFLD, and the "multiple hit" hypothesis considers multiple insults acting together on genetically predisposed subjects to induceNAFLD and provides a more accurate explanation of NAFLd pathogenesis.
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TL;DR: It is not clear whether NAFLD causes metabolic dysfunction or whether metabolic dysfunction is responsible for IHTG accumulation, or possibly both, but it is likely that abnormalities in fatty acid metabolism are key factors involved in the development of insulin resistance, dyslipidemia, and other cardiometabolic risk factors associated withNAFLD.
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Renata Belfort,Stephen A. Harrison,Kenneth A. Brown,Celia Darland,Joan Finch,Jean Hardies,Bogdan Balas,Amalia Gastaldelli,Amalia Gastaldelli,Fermin O. Tio,Joseph P. Pulcini,Rachele Berria,Jennie Z. Ma,Sunil Dwivedi,Russell Havranek,Chris Fincke,Ralph A. DeFronzo,George A. Bannayan,Steven Schenker,Kenneth Cusi +19 more
TL;DR: In this proof-of-concept study, the administration of pioglitazone led to metabolic and histologic improvement in subjects with nonalcoholic steatohepatitis and larger controlled trials of longer duration are warranted to assess the long-term clinical benefit.
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Energy metabolism in the liver
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TL;DR: This review focuses on the role of several adipokines associated with obesity and the potential impact on obesity-related metabolic diseases.
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