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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Nonalcoholic fatty liver disease: From steatosis to cirrhosis
TL;DR: The present “gold standard” management of NASH is modest weight reduction, particularly correction of central obesity achieved by combining dietary measures with increased physical activity, which improves insulin resistance and reverses steatosis, hepatocellular injury, inflammation, and fibrosis.
References
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Journal ArticleDOI
Globular Adiponectin Protected ob/ob Mice from Diabetes and ApoE-deficient Mice from Atherosclerosis
Toshimasa Yamauchi,Junji Kamon,Hironori Waki,Yasushi Imai,Nobuhiro Shimozawa,K. Hioki,S. Uchida,Yusuke Ito,Keisuke Takakuwa,Junji Matsui,Makoto Takata,Kazuhiro Eto,Yasuo Terauchi,Kajuro Komeda,Masaki Tsunoda,Koji Murakami,Yasuyuki Ohnishi,Takeshi Naitoh,Ken Ichi Yamamura,Yoshito Ueyama,Philippe Froguel,Satoshi Kimura,A. Ryozo Nagai,Takashi Kadowaki +23 more
TL;DR: It is shown that replenishment of globular adiponectin may provide a novel treatment modality for both type 2 diabetes and atherosclerosis, and this is the first demonstration that globular leptin can protect against Atherosclerosis in vivo.
Journal ArticleDOI
Endogenous glucose production is inhibited by the adipose-derived protein Acrp30
TL;DR: Results indicate that an acute increase in circulating Acrp30 levels lowers hepatic glucose production without affecting peripheral glucose uptake, and a moderate rise in circulating levels of the adipose-derived protein Acp30 inhibits both the expression of hepatic gluconeogenic enzymes and the rate of endogenous glucose production.
Journal ArticleDOI
Cytokines in Alcoholic and Nonalcoholic Steatohepatitis
Herbert Tilg,Anna Mae Diehl +1 more
TL;DR: In most tissues, including the liver, constitutive production of cytokines is absent or minimal, but as physiologic and pathologic stimuli activate cells, the production of these autocrine, paracrine, and endocrine effector molecules increases, and they, in turn, orchestrate the tissue's response to the stimulus.
Journal ArticleDOI
Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease
Zhiping Li,Shiqi Yang,Huizhi Lin,Jiawen Huang,Paul A. Watkins,Paul A. Watkins,Ann B. Moser,Ann B. Moser,Claudio DeSimone,Xiao Yu Song,Anna Mae Diehl +10 more
TL;DR: The concept that intestinal bacteria induce endogenous signals that play a pathogenic role in hepatic insulin resistance and NAFLD are supported and novel therapies for these common conditions are suggested.
Journal ArticleDOI
The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor
TL;DR: It is suggested that TNFs--which control many aspects of inflammation, adaptive immunity, apoptosis and energy homeostasis--arose by divergence from a primordial recognition molecule of the innate immune system.
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