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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Journal ArticleDOI
Histopathology of pediatric nonalcoholic fatty liver disease.
Jeffrey B. Schwimmer,Jeffrey B. Schwimmer,Cynthia Behling,Robert O. Newbury,Reena Deutsch,Caroline M. Nievergelt,Nicholas J. Schork,Joel E. Lavine,Joel E. Lavine +8 more
TL;DR: Type 1 and type 2 NASH are distinct subtypes of pediatric NAFLD, andtype 2 is the most common pattern in children, and NASH subtypes should be considered when interpreting liver biopsies and planning studies of the pathophysiology, genetics, natural history, or response to treatment in pediatricNAFLD.
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Mitochondrial dysfunction in NASH: causes, consequences and possible means to prevent it.
TL;DR: There is accumulating evidence that mitochondrial dysfunction (more particularly respiratory chain deficiency) plays a key role in the physiopathology of NASH whatever its initial cause and that several drugs can prevent or even reverse NASH.
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Adiponectin: action, regulation and association to insulin sensitivity
TL;DR: Adiponectin in addition to possible anti‐inflammatory and anti‐atherogenic effects appears to be an insulin enhancer, with potential as a new pharmacologic treatment modality of the metabolic syndrome and type 2 diabetes.
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Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies.
Prasenjit Manna,Sushil K. Jain +1 more
TL;DR: The role of oxidative stress in the pathogenesis of obesity and its associated risk factors, the role of dysfunctional adipose tissue in development of these risk Factors, and potential strategies to regulate body weight loss/gain for better health benefits are highlighted.
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Adiponectin--a key adipokine in the metabolic syndrome.
Jonathan P. Whitehead,Ayanthi A. Richards,Ingrid J. Hickman,Graeme A. Macdonald,Johannes B. Prins +4 more
TL;DR: Given the low levels of adiponectin in subjects with the metabolic syndrome, and the beneficial effect of the adipokine in animal studies, there is exciting potential for adiponECTin replacement therapy in insulin resistance and related disorders.
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