PRL-releasing peptide interacts with leptin to reduce food intake and body weight.
PRL-releasing peptide (PrRP) is a novel anorexigen that reduces food intake and body weight gain in rats. In common with other anorexigens, PrRP mRNA expression is reduced during states of negative energy balance, i.e. lactation and fasting in female rats. In this study, we examined the interaction between PrRP and the adiposity signal, leptin, which interacts with a number of peptidergic systems in the brain to regulate energy homeostasis. Intracerebroventricular coadministration of 4 nmol PrRP and 1 microg leptin in rats resulted in additive reductions in nocturnal food intake and body weight gain and an increase in core body temperature compared with each peptide alone. We show also, by quantitative in situ hybridization, that PrRP mRNA is reduced in fasted male rats and obese Zucker rats, indicating that PrRP mRNA expression, like that of other anorexigens, may be regulated by leptin. Finally we show, using immunohistochemistry, that greater than 90% of PrRP neurons in all regions where PrRP is expressed contain leptin receptors. Thus, we provide evidence for PrRP neurons forming part of the leptin-sensitive brain circuitry involved in the regulation of food intake and energy homeostasis.
Ellacott
Kate L J
KL
School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom.
Lawrence
Catherine B
CB
Rothwell
Nancy J
NJ
Luckman
Simon M
SM
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects*; D003864:Depression, Chemical; D004302:Dorsomedial Hypothalamic Nucleus / Q000378:metabolism; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects; D019084:Fluorescent Antibody Technique, Indirect; D007028:Hypothalamic Hormones / Q000008:administration & dosage / Q000494:pharmacology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007276:Injections, Intraventricular; D020738:Leptin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology*; D009765:Obesity / Q000235:genetics; D011388:Prolactin / Q000378:metabolism; D056690:Prolactin-Releasing Hormone; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D017552:Solitary Nucleus / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D014697:Ventromedial Hypothalamic Nucleus / Q000378:metabolism
D007028:Hypothalamic Hormones; D020738:Leptin; D009479:Neuropeptides; C534379:Prlh protein, rat; D056690:Prolactin-Releasing Hormone; D011388:Prolactin; D014446:Tyrosine 3-Monooxygenase