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
More filters
Journal ArticleDOI
The expanding role of fish models in understanding non-alcoholic fatty liver disease
TL;DR: How small fish are increasingly being used to uncover factors that contribute to normal hepatic lipid metabolism is discussed, and how these easily manipulated organisms have been used to evaluate the therapeutic effectiveness of various chemical compounds for the treatment of NAFLD.
Journal ArticleDOI
Ethanol and liver: recent insights into the mechanisms of ethanol-induced fatty liver.
TL;DR: Clinical studies evaluating combination therapy of carvedilol with a TNF-α inhibitor to treat patients with AFLD are warranted to prevent the development of alcoholic liver disease.
Journal ArticleDOI
Adiponectin: protection of the endothelium.
Karen S.L. Lam,Aimin Xu +1 more
TL;DR: The various mechanisms through which adiponectin may protect the endothelium, via its insulin-sensitizing, antiatherogenic, anti-inflammatory, and antioxidant properties, are reviewed.
Journal ArticleDOI
Adiponectin as a target for the treatment of nonalcoholic steatohepatitis with thiazolidinediones: A systematic review.
TL;DR: These results warrant further consideration of TZDs, but even more importantly point to a key role for novel potential treatments for NASH patients such as the newer selective peroxisome proliferator activated receptor-γ modulators, which increase adiponectin without significant weight gain.
Journal ArticleDOI
Cellular basis of hepatic fibrosis and its role in inflammation and cancer.
TL;DR: The altered extracellular matrix (ECM) provides a permissive milieu for the development of cellular dysplasia and ultimately hepatocellular carcinoma (HCC) and new advances in therapeutic options for patients with chronic liver disease are emerging.
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.
Related Papers (5)
Cloning of adiponectin receptors that mediate antidiabetic metabolic effects
Toshimasa Yamauchi,Junji Kamon,Yusuke Ito,Atsushi Tsuchida,Takehiko Yokomizo,Takehiko Yokomizo,Shunbun Kita,Takuya Sugiyama,Makoto Miyagishi,Makoto Miyagishi,Kazuo Hara,Masaki Tsunoda,Koji Murakami,Toshiaki Ohteki,S. Uchida,Sato Takekawa,Hironori Waki,Nelson H. Tsuno,Yoichi Shibata,Yasuo Terauchi,Philippe Froguel,Kazuyuki Tobe,Shigeo Koyasu,Kazunari Taira,Kazunari Taira,Toshio Kitamura,Takao Shimizu,Takao Shimizu,Ryozo Nagai,Takashi Kadowaki +29 more
Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase
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
Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity.
Yukio Arita,Shinji Kihara,Noriyuki Ouchi,Masahiko Takahashi,Kazuhisa Maeda,Jun-ichiro Miyagawa,Kikuko Hotta,Iichiro Shimomura,Tadashi Nakamura,Koji Miyaoka,Hiroshi Kuriyama,Makoto Nishida,Shizuya Yamashita,Kosaku Okubo,Kenji Matsubara,Masahiro Muraguchi,Yasuichi Ohmoto,Tohru Funahashi,Yuji Matsuzawa +18 more