The NPY/AgRP neuron and energy homeostasis.
Kennedy hypothesized nearly 50 y ago that negative feedback regulation of body fat stores involves hormones that circulate in proportion to adiposity and enter the brain, where they exert inhibitory effects on food intake and energy balance. Recent studies implicate leptin and insulin as 'adiposity signals' to the brain that promote negative energy balance in two ways: by inhibiting 'anabolic' hypothalamic neuronal circuits that stimulate food intake and promote weight gain, and by activating 'catabolic' pathways that reduce food intake and body weight. Chief among candidate 'anabolic' effector pathways is the NPY/AgRP neuron, found only in the hypothalamic arcuate nucleus. These neurons make peptides that potently stimulate food intake not only by increasing neuropeptide Y (NPY) signaling, but by reducing melanocortin signaling via the release of agouti-related peptide (AgRP), an endogenous melanocortin 3/4 receptor antagonist. Since NPY/AgRP neurons express receptors for leptin and insulin and are inhibited by these hormones, they are activated by a decrease of leptin or insulin signaling. Fasting, uncontrolled diabetes, and genetic leptin deficiency are examples of conditions in which food intake increases via a mechanism hypothesized to involve NPY/AgRP neurons. Data are reviewed which illustrate the role of these neurons in adaptive and maladaptive states characterized by hyperphagia and weight gain.
Morton
G J
GJ
Department of Medicine, Harborview Medical Center and University of Washington, Seattle, Washington 98104, USA.
Schwartz
M W
MW
D000273:Adipose Tissue / Q000502:physiology; D054369:Agouti-Related Protein; D000818:Animals; D004734:Energy Metabolism; D005246:Feedback; D006706:Homeostasis; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D009474:Neurons / Q000502:physiology*; D009478:Neuropeptide Y / Q000502:physiology*; D011506:Proteins / Q000502:physiology*
D054369:Agouti-Related Protein; D036341:Intercellular Signaling Peptides and Proteins; D009478:Neuropeptide Y; D011506:Proteins