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
Hepatic Steatosis as a Marker of Metabolic Dysfunction
Elisa Fabbrini,Faidon Magkos +1 more
TL;DR: Understanding the factors involved in the pathogenesis and pathophysiology of NAFLD will lead to a better understanding of the mechanisms responsible for the metabolic complications of obesity, and hopefully to the discovery of novel effective treatments for their reversal.
Journal ArticleDOI
Lipotoxicity: effects of dietary saturated and transfatty acids
Debora Estadella,Claudia Maria Oller do Nascimento,Lila M. Oyama,Eliane Beraldi Ribeiro,Ana Raimunda Dâmaso,Aline de Piano +5 more
TL;DR: The focus of this paper was to elucidate the influence of dietary SFA and TFA intake on the promotion of lipotoxicity to the liver and cardiovascular, endothelial, and gut microbiota systems, as well as on insulin resistance and endoplasmic reticulum stress.
Journal ArticleDOI
Keynote review: The adipocyte as a drug discovery target
TL;DR: Various areas of adipocyte physiology that have not yet been explored pharmacologically are highlighted and some of the limitations associated with these pharmacotherapies are emphasized.
Journal ArticleDOI
Regulation of fat metabolism in the liver: link to non-alcoholic hepatic steatosis and impact of physical exercise
TL;DR: Physical exercise would interfere with the development of hepatic steatosis by stimulating lipid oxidation and inhibiting lipid synthesis in liver through the activation of the AMP-activated protein kinase pathway.
Journal ArticleDOI
Roles of Chemokines and Chemokine Receptors in Obesity-Associated Insulin Resistance and Nonalcoholic Fatty Liver Disease.
TL;DR: The present review highlights chemokines and chemokine receptors as key contributing factors that link obesity to insulin resistance, T2DM, and NAFLD.
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