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
Adipokines in inflammation and metabolic disease
TL;DR: The role of adipokines in inflammatory responses is focused on and their potential as regulators of metabolic function is discussed.
Journal ArticleDOI
Inflammatory Mechanisms in Obesity
TL;DR: The discovery that obesity itself results in an inflammatory state in metabolic tissues ushered in a research field that examines the inflammatory mechanisms in obesity, and metaflammation is summarized, defined as low-grade, chronic inflammation orchestrated by metabolic cells in response to excess nutrients and energy.
Journal ArticleDOI
Adipocytokines: mediators linking adipose tissue, inflammation and immunity.
TL;DR: Several adipocytokines have a central role in the regulation of insulin resistance, as well as many aspects of inflammation and immunity, and understanding this rapidly growing family of mainly adipocyte-derived mediators might be of importance in the development of new therapies for obesity-associated diseases.
Journal ArticleDOI
Adiponectin and Adiponectin Receptors
TL;DR: It is shown that AdipoR1 and AdIPoR2 serve as receptors for globular and full-length adiponectin and mediate increased AMP-activated protein kinase, peroxisome proliferator-activated receptor-alpha ligand activities, and glucose uptake and fatty-acid oxidation by adiponECTin.
Journal ArticleDOI
Nonalcoholic fatty liver disease: From steatosis to cirrhosis
TL;DR: The present “gold standard” management of NASH is modest weight reduction, particularly correction of central obesity achieved by combining dietary measures with increased physical activity, which improves insulin resistance and reverses steatosis, hepatocellular injury, inflammation, and fibrosis.
References
More filters
Journal ArticleDOI
Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity.
Christi A. Matteoni,Zobair M. Younossi,Terry Gramlich,Navdeep Boparai,Yao Chang Liu,Arthur J. McCullough +5 more
TL;DR: The outcome of cirrhosis and liver-related death is not uniform across the spectrum of nonalcoholic fatty liver, and poor outcomes are more frequent in patients in whom biopsies show ballooning degeneration and Mallory hyaline or fibrosis.
Journal ArticleDOI
The adipocyte-secreted protein Acrp30 enhances hepatic insulin action
TL;DR: It is proposed that Acrp30 is a potent insulin enhancer linking adipose tissue and whole-body glucose metabolism, which triggers a transient decrease in basal glucose levels in mice treated with streptozotocin.
Journal ArticleDOI
AdipoQ is a novel adipose-specific gene dysregulated in obesity.
TL;DR: The tissue-specific expression of a putative secreted protein suggests that this factor may function as a novel signaling molecule for adipose tissue.
Journal ArticleDOI
Novel Modulator for Endothelial Adhesion Molecules: Adipocyte-Derived Plasma Protein Adiponectin
Noriyuki Ouchi,Shinji Kihara,Yukio Arita,Kazuhisa Maeda,Hiroshi Kuriyama,Yoshihisa Okamoto,Kikuko Hotta,Makoto Nishida,Masahiko Takahashi,Tadashi Nakamura,Shizuya Yamashita,Tohru Funahashi,Yuji Matsuzawa +12 more
TL;DR: Observations suggest that adiponectin modulates endothelial inflammatory response and that the measurement of plasma adiponECTin levels may be helpful in assessment of CAD risk.
Journal ArticleDOI
Diet-induced insulin resistance in mice lacking adiponectin/ACRP30.
Norikazu Maeda,Iichiro Shimomura,Ken Kishida,Hitoshi Nishizawa,Morihiro Matsuda,Hiroyuki Nagaretani,Naoki Furuyama,Hidehiko Kondo,Masahiko Takahashi,Yukio Arita,Ryutaro Komuro,Noriyuki Ouchi,Shinji Kihara,Yoshihiro Tochino,Keiichi Okutomi,Masato Horie,Satoshi Takeda,Toshifumi Aoyama,Tohru Funahashi,Yuji Matsuzawa +19 more
TL;DR: The results indicate that adiponectin/ACRP30 deficiency and high TNF-α levels in KO mice reduced muscle FATP-1 mRNA and IRS-1-mediated insulin signaling, resulting in severe diet-induced insulin resistance.
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