Peptide YY signaling in the lateral parabrachial nucleus increases food intake through the Y1 receptor.
Although central PYY delivery potently increases food intake, the sites of action and mechanisms mediating these hyperphagic effects are not fully understood. The present studies investigate the contribution of lateral parabrachial nucleus (lPBN) PYY-Y receptor signaling to food intake control, as lPBN neurons express Y receptors and receive PYY fibers and are known to integrate circulating and visceral sensory signals to regulate energy balance. Immunohistochemical results identified a subpopulation of gigantocellular reticular nucleus PYY-producing neurons that project monosynaptically to the lPBN, providing an endogenous source of PYY to the lPBN. lPBN microinjection of PYY-(1-36) or PYY-(3-36) markedly increased food intake by increasing meal size. To determine which receptors mediate these behavioral results, we first performed quantitative real-time PCR to examine the relative levels of Y receptor expression in lPBN tissue. Gene expression analyses revealed that, while Y1, Y2, and Y5 receptors are each expressed in lPBN tissue, Y1 receptor mRNA is expressed at fivefold higher levels than the others. Furthermore, behavioral/pharmacological results demonstrated that the hyperphagic effects of PYY-(3-36) were eliminated by lPBN pretreatment with a selective Y1 receptor antagonist. Together, these results highlight the lPBN as a novel site of action for the intake-stimulatory effects of central PYY-Y1 receptor signaling.
Department of Psychology, University of Pennsylvania, Philadelphia, Pennsylvania; and amberla@sas.upenn.edu.
Amber L
AL
Alhadeff
Department of Psychology, University of Pennsylvania, Philadelphia, Pennsylvania; and.
Danielle
D
Golub
Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania.
Matthew R
MR
Hayes
Department of Psychology, University of Pennsylvania, Philadelphia, Pennsylvania; and.
Harvey J
HJ
Grill
D000818:Animals; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008845:Microinjections; D065823:Parabrachial Nucleus / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D019894:Peptide YY / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D017476:Receptors, Neuropeptide Y / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism
D010446:Peptide Fragments; D012333:RNA, Messenger; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor; C100568:neuropeptide Y5 receptor; D019894:Peptide YY; C061785:peptide YY (3-36); C514549:peptide YY (1-36)
Y1 receptor; food intake; gigantocellular reticular nucleus; obesity; parabrachial nucleus; peptide YY