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
agoutirelated peptide (AGRP), and those that express proopiomelanocortin (POMC), the
precursor of the catabolic peptide, αMSH. 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 AGRR 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.
Key words
Food Intake - Obesity - Body Weight - Arcuate Nucleus - NPY - POMC
