Adiponectin stimulates AMP-activated protein kinase in the hypothalamus and increases food intake

Naoto Kubota; Wataru Yano; Tetsuya Kubota; Toshimasa Yamauchi; Shinsuke Itoh; Hiroki Kumagai; Hideki Kozono; Iseki Takamoto; Shiki Okamoto; Tetsuya Shiuchi; Ryo Suzuki; Hidemi Satoh; Atsushi Tsuchida; Masao Moroi; Kaoru Sugi; Tetsuo Noda; Hiroyuki Ebinuma; Yoichi Ueta; Tatsuya Kondo; Eiichi Araki; Osamu Ezaki; Ryozo Nagai; Kazuyuki Tobe; Yasuo Terauchi; Kohjiro Ueki; Yasuhiko Minokoshi; Takashi Kadowaki

doi:10.1016/j.cmet.2007.06.003

Adiponectin stimulates AMP-activated protein kinase in the hypothalamus and increases food intake

Cell Metab. 2007 Jul;6(1):55-68. doi: 10.1016/j.cmet.2007.06.003.

Affiliation

¹ Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

PMID: 17618856
DOI: 10.1016/j.cmet.2007.06.003

Abstract

Adiponectin has been shown to stimulate fatty acid oxidation and enhance insulin sensitivity through the activation of AMP-activated protein kinase (AMPK) in the peripheral tissues. The effects of adiponectin in the central nervous system, however, are still poorly understood. Here, we show that adiponectin enhances AMPK activity in the arcuate hypothalamus (ARH) via its receptor AdipoR1 to stimulate food intake; this stimulation of food intake by adiponectin was attenuated by dominant-negative AMPK expression in the ARH. Moreover, adiponectin also decreased energy expenditure. Adiponectin-deficient mice showed decreased AMPK phosphorylation in the ARH, decreased food intake, and increased energy expenditure, exhibiting resistance to high-fat-diet-induced obesity. Serum and cerebrospinal fluid levels of adiponectin and expression of AdipoR1 in the ARH were increased during fasting and decreased after refeeding. We conclude that adiponectin stimulates food intake and decreases energy expenditure during fasting through its effects in the central nervous system.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

AMP-Activated Protein Kinases
Adenoviridae / genetics
Adiponectin / cerebrospinal fluid
Adiponectin / genetics
Adiponectin / physiology*
Adipose Tissue, White / cytology
Adipose Tissue, White / metabolism
Animals
Arcuate Nucleus of Hypothalamus / metabolism
Eating*
Energy Metabolism
Female
Hypothalamus / enzymology*
Hypothalamus / pathology
Immunoenzyme Techniques
In Situ Hybridization
Leptin / metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Multienzyme Complexes / genetics
Multienzyme Complexes / metabolism*
Phosphorylation
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism*
RNA Probes
Receptors, Adiponectin
Receptors, Cell Surface / antagonists & inhibitors
Receptors, Cell Surface / genetics
Receptors, Cell Surface / metabolism
Receptors, Leptin

Substances

Adiponectin
Leptin
Multienzyme Complexes
RNA Probes
Receptors, Adiponectin
Receptors, Cell Surface
Receptors, Leptin
adiponectin receptor 1, mouse
Protein Serine-Threonine Kinases
AMP-Activated Protein Kinases