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
Pathophysiology of nonalcoholic steatohepatitis.
TL;DR: As is the case for other common complex metabolic diseases, it is the interaction between the environment and genetics that will determine the phenotypic expression of NAFLD and NASH in each individual patient.
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Molecular basis and mechanisms of progression of non-alcoholic steatohepatitis
TL;DR: Recent developments regarding the basic mechanisms of NASH development are reviewed, including accumulation of triglycerides in the hepatocytes is the result of increased inflow of free fatty acids and de novo lipogenesis.
Journal ArticleDOI
The role of AMP-activated protein kinase in the action of ethanol in the liver.
TL;DR: The findings suggest that AMPK may play a key role in regulating the effects of ethanol on SREBP-1 activation, fatty acid metabolism, and development of alcoholic fatty liver.
Journal ArticleDOI
Adiponectin and its receptors in non-alcoholic steatohepatitis
Susanne Kaser,Alexander R. Moschen,A. Cayon,Arthur Kaser,Javier Crespo,Fernando Pons-Romero,Christoph Ebenbichler,J. R. Patsch,Herbert Tilg +8 more
TL;DR: Low liver expression of adiponectin and its receptors in morbidly obese patients undergoing bariatric surgery might be of pathophysiological relevance in non-alcoholic fatty liver diseases.
References
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The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity
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TL;DR: It is concluded that decreased adiponectin is implicated in the development of insulin resistance in mouse models of both obesity and lipoatrophy and that the replenishment of adiponECTin might provide a novel treatment modality for insulin resistance and type 2 diabetes.
Journal ArticleDOI
Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase
Toshimasa Yamauchi,Junji Kamon,Yasuhiko Minokoshi,Yoichi M. Ito,Hironori Waki,S. Uchida,Shigeo Yamashita,Mitsuhiko Noda,Shunbun Kita,K Ueki,Koji Eto,Y. Akanuma,Philippe Froguel,Fabienne Foufelle,Pascal Ferré,David Carling,Shigeko Kimura,Ryozo Nagai,Barbara B. Kahn,Takashi Kadowaki +19 more
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Plasma Concentrations of a Novel, Adipose-Specific Protein, Adiponectin, in Type 2 Diabetic Patients
Kikuko Hotta,Tohru Funahashi,Yukio Arita,Masahiko Takahashi,Morihiro Matsuda,Yoshihisa Okamoto,Hiromi Iwahashi,Hiroshi Kuriyama,Noriyuki Ouchi,Kazuhisa Maeda,Makoto Nishida,Shinji Kihara,Naohiko Sakai,Tadahisa Nakajima,Kyoichi Hasegawa,Masahiro Muraguchi,Yasukazu Ohmoto,Tadashi Nakamura,Shizuya Yamashita,Toshiaki Hanafusa,Yuji Matsuzawa +20 more
TL;DR: Results suggest that the decreased plasma adiponectin concentrations in diabetes may be an indicator of macroangiopathy, and weight reduction significantly elevated plasma adip onectin levels in the diabetic subjects as well as the nondiabetic subjects.
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