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.

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