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 homolog osmotin, a potential anti-obesity compound, suppresses abdominal fat accumulation in C57BL/6 mice on high-fat diet and in 3T3-L1 adipocytes.
TL;DR: The results provide the first indication that osmotin exerts therapeutic effects on obesity, which could promote development of therapeutic aspects for obesity and related diseases.
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The medical complications of alcohol use: understanding mechanisms to improve management
TL;DR: Genetic susceptibility to tissue injury is explored and the reasons why many heavy drinkers do not appear to experience organ damage are considered, and approaches to the management of certain alcohol-related disorders are outlined.
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Influence of insulin resistance and adipocytokines on elevated serum alanine aminotransferase in obese patients.
TL;DR: Some metabolic parameters are associated with elevated ALT in obese female patients, however, adjusted by other variables, only insulin resistance remained associated.
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Long-term globular adiponectin administration improves adipose tissue dysmetabolism in high-fat diet-fed Wistar rats.
Paulo Matafome,Tiago Rodrigues,Ana Margarida Pereira,Liliana Letra,H Azevedo,A Paixão,M Silvério,Almeida Ab,Cristina M. Sena,Raquel Seiça +9 more
TL;DR: Long-term globular adiponectin administration was able to improve pathways of insulin signalling and lipid storage in adipose tissue of high-fat diet-fed rats, contributing to a better metabolic profile.
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T cell–mediated hepatic inflammation modulates adiponectin levels in mice: role of tumor necrosis factor α
Alison M. Morris,Joseph A. Sennello,Raja Fayad,Robert H. Eckel,Charles A. Dinarello,Giamila Fantuzzi +5 more
TL;DR: It is shown that inflammation-induced TNF-α is a critical mediator of adipose-tissue-derived adiponectin in vivo and this was associated with restored circulating levels of adiponECTin.
References
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Atherosclerosis — An Inflammatory Disease
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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.
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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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