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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Adiponectin deficiency impairs liver regeneration through attenuating STAT3 phosphorylation in mice
Run-Zhe Shu,Feng Zhang,Fang Wang,De-Chun Feng,Xi-Hua Li,Wei-hua Ren,Xiao-lin Wu,Xue Yang,Xiaodong Liao,Lei Huang,Zhugang Wang,Zhugang Wang +11 more
TL;DR: Increased expression of Socs3 and subsequently reduced activation of STAT3 in adiponectin-null mice may contribute to the alteration of the liver regeneration capability and hepatic lipid metabolism after PH.
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Hypoadiponectinemia and insulin resistance are associated with nonalcoholic fatty liver disease.
Dokyoung Yoon,Seung Hwan Lee,Hye Soon Park,Ji Hoon Lee,Jin Seo Park,Kyung Hwan Cho,Seon Mee Kim +6 more
TL;DR: It is demonstrated that hypoadiponectinemia and insulin resistance are associated with NAFLD independent of obesity.
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Endocrine Diseases and the Liver
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Impaired adipogenic response to thiazolidinediones in mice expressing human apolipoproteinE4
TL;DR: It is concluded that the effects of TZDs are APOE isoform dependent, and that the metabolic damage observed in APOE4 mice is rooted in an impaired activation of the adipogenic program in the adipose tissues expressing APOE 4.
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The association between adipocytokines and biomarkers for nonalcoholic fatty liver disease-induced liver injury: a study in the general population.
Shira Zelber-Sagi,Vlad Ratziu,Izabel Zvibel,Ilana Goldiner,Laurie Blendis,Gilles Morali,Zamir Halpern,Ran Oren +7 more
TL;DR: Low adiponectin and high leptin and the combination of both have a strong independent association with presumed early-stage NASH, however, early- stage fibrosis cannot be predicted by these adipocytokines.
References
More filters
Journal ArticleDOI
Atherosclerosis — An Inflammatory Disease
TL;DR: Atherosclerosis is an inflammatory disease as discussed by the authors, and it is a major cause of death in the United States, Europe, and much of Asia, despite changes in lifestyle and use of new pharmacologic approaches to lower plasma cholesterol concentrations.
Journal ArticleDOI
The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity
Toshimasa Yamauchi,Junji Kamon,Hironori Waki,Yasuo Terauchi,Naoto Kubota,Kazuo Hara,Y. Mori,Tomohiro Ide,Kouji Murakami,Nobuyo Tsuboyama-Kasaoka,Osamu Ezaki,Y. Akanuma,Oksana Gavrilova,Charles Vinson,Marc L. Reitman,Hiroyuki Kagechika,Koichi Shudo,Madoka Yoda,Yasuko Nakano,Kazuyuki Tobe,R. Nagai,Shigeko Kimura,Motowo Tomita,Philippe Froguel,Takashi Kadowaki +24 more
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
TL;DR: It is shown that phosphorylation and activation of the 5′-AMP-activated protein kinase (AMPK) are stimulated with globular and full-length Ad in skeletal muscle and only with full- lengths Ad in the liver, indicating that stimulation of glucose utilization and fatty-acid oxidation by Ad occurs through activation of AMPK.
Journal ArticleDOI
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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