Leptin sensitive neurons in the hypothalamus.
A major paradigm in the field of obesity research is the existence of an adipose tissue-brain endocrine axis for the regulation of body weight. Leptin, the peptide mediator of this axis, is secreted by adipose cells. It lowers food intake and body weight by acting in the hypothalamus, a region expressing an abundance of leptin receptors and a variety of neuropeptides that influence food intake and energy balance. Among the most promising candidates for leptin-sensitive cells in the hypothalamus are arcuate nucleus neurons that co-express the anabolic neuropeptides, neuropeptide Y (NPY) and agouti-related peptide (AGRP), and those that express proopiomelanocortin (POMC), the precursor of the catabolic peptide, alphaMSH. These cell types contain mRNA encoding leptin receptors and show changes in neuropeptide gene expression in response to changes in food intake and circulating leptin levels. Decreased leptin signaling in the arcuate nucleus is hypothesized to increase the expression of NPY and AGRP. Levels of leptin receptor mRNA and leptin binding are increased in the arcuate nucleus during fasting, principally in NPY/AGRP neurons. These findings suggest that changes in leptin receptor expression in the arcuate nucleus are inversely associated with changes in leptin signaling, and that the arcuate nucleus is an important target of leptin action in the brain.
Baskin
D G
DG
VA Puget Sound Health Care System, Department of Medicine, University of Washington School of Medicine, Seattle 98108-1597, USA. baskindg@u.washington.edu
Hahn
T M
TM
Schwartz
M W
MW
D054369:Agouti-Related Protein; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology; D006801:Humans; D007031:Hypothalamus / Q000166:cytology*; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D009478:Neuropeptide Y / Q000502:physiology; D011333:Pro-Opiomelanocortin / Q000502:physiology; D011506:Proteins / Q000494:pharmacology* / Q000502:physiology
D054369:Agouti-Related Protein; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D009478:Neuropeptide Y; D011506:Proteins; D011333:Pro-Opiomelanocortin