Chronic neuropeptide Y infusion into the lateral ventricle induces sustained feeding and obesity in mice lacking either Npy1r or Npy5r expression.
Neuropeptide Y (NPY) is a powerful orexigenic neurotransmitter. The NPY Y1 and Y5 receptors have been implicated in mediating the appetite-stimulating activity of NPY. To further investigate the importance of these two receptors in NPY-induced hyperphagia after chronic central administration, we used mice lacking either Npy1r or Npy5r expression. NPY infusion into the lateral ventricle of wild-type mice stimulated food intake and induced obesity over a 7-d period. Fat pad weight as well as plasma insulin, leptin, and corticosterone levels were strongly increased in NPY-treated mice. In addition, NPY infusion resulted in a significant decrease in hypothalamic NPY and proopiomelanocortin expression. Interestingly, the lack of either Npy1r or Npy5r expression in knockout mice did not affect such feeding response to chronic NPY infusion. Moreover, the obesity syndrome that developed in these animals was similar to that in wild-type animals. Taken together, these data strongly suggest biological redundancies between Y1 and Y5 receptor signaling in the NPY-mediated control of food intake.
Raposinho
Paula D
PD
Division of Pediatric Endocrinology and Diabetology, University of Geneva School of Medicine, 1211 Geneva 14, Switzerland.
Pedrazzini
Thierry
T
White
Richard B
RB
Palmiter
Richard D
RD
Aubert
Michel L
ML
D000273:Adipose Tissue / Q000033:anatomy & histology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects*; D006963:Hyperphagia / Q000139:chemically induced; D007276:Injections, Intraventricular; D007328:Insulin / Q000097:blood; D020547:Lateral Ventricles; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009478:Neuropeptide Y / Q000235:genetics / Q000494:pharmacology*; D009765:Obesity / Q000503:physiopathology*; D011333:Pro-Opiomelanocortin / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D017476:Receptors, Neuropeptide Y / Q000235:genetics*
D007328:Insulin; D020738:Leptin; D009478:Neuropeptide Y; D012333:RNA, Messenger; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C100568:neuropeptide Y5 receptor; D011333:Pro-Opiomelanocortin; D003345:Corticosterone