Integration of NPY, AGRP, and melanocortin signals in the hypothalamic paraventricular nucleus: evidence of a cellular basis for the adipostat.
Energy stores are held relatively constant in many mammals. The circuitry necessary for maintaining energy homeostasis should (1) sense the amount of energy stored in adipose tissue, (2) sense and integrate the multiple opposing signals regarding nutritional state, and (3) provide output regulating energy intake and expenditure to maintain energy homeostasis. We demonstrate that individual neurons within the paraventricular nucleus of the hypothalamus (PVH) are capable of detection and integration of orexigenic (neuropeptide Y [NPY]) and anorexigenic (melanocortin) signals, that NPY and melanocortins are functional antagonists of each other within the PVH in the regulation of feeding behavior, and that melanocortin administration within the PVH regulates both feeding behavior and energy expenditure. These data provide a cellular basis for the adipostat within neurons in the PVH that appear to be jointly regulated by NPY- and melanocortin-responsive neurons.
Cowley
M A
MA
Vollum Institute, Oregon Health Sciences University, Portland 97201, USA.
Pronchuk
N
N
Fan
W
W
Dinulescu
D M
DM
Colmers
W F
WF
Cone
R D
RD
D054369:Agouti-Related Protein; D000818:Animals; D004553:Electric Conductivity; D036341:Intercellular Signaling Peptides and Proteins; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000737:chemistry / Q000502:physiology; D009478:Neuropeptide Y / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D011333:Pro-Opiomelanocortin / Q000032:analysis; D011506:Proteins / Q000032:analysis / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D044105:Receptor, Melanocortin, Type 4; D018000:Receptors, Peptide / Q000032:analysis / Q000502:physiology*; D000521:alpha-MSH / Q000031:analogs & derivatives / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D054369:Agouti-Related Protein; D036341:Intercellular Signaling Peptides and Proteins; D009478:Neuropeptide Y; D011506:Proteins; D044105:Receptor, Melanocortin, Type 4; D018000:Receptors, Peptide; C081720:alpha-MSH (4-10)amide, Ac-Nle(4)-cyclo(Asp(5)-Phe(7)-Lys(10))-; D005680:gamma-Aminobutyric Acid; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin