Repeated administration of the anorectic factor prolactin-releasing peptide leads to tolerance to its effects on energy homeostasis.
Central administration of a single dose of prolactin-releasing peptide (PrRP) causes a reduction in both fast-induced and nocturnal food intake and body weight gain. The aim of this study was to examine the effect of repeated administration of PrRP on energy homeostasis, including a measure of the expression of the mitochondrial uncoupling protein-1 (UCP-1) in brown adipose tissue. Conscious, free-feeding animals received central injections of PrRP (4 nmol icv) or vehicle. A single injection at 1000 caused a sustained hyperthermia over the 4-h test period and an increase in the expression of UCP-1 mRNA. Repeated, twice daily injection caused a reduction in body weight gain greater than that seen in pair-fed animals for the first 48-72 h. After 72 h, the animals became refractory to the actions of PrRP. The pair-fed group showed a reduction in UCP-1 mRNA expression at 48 h, which was reversed by PrRP treatment. This study indicates that PrRP exerts its effects on energy homeostasis in the short-medium term by reducing food intake and increasing energy expenditure.
Ellacott
Kate L J
KL
1.124 Stopford Bldg., School of Biological Sciences, Univ. of Manchester, Oxford Road, Manchester, M13 9PT UK. simon.luckman@man.ac.uk
Lawrence
Catherine B
CB
Pritchard
Lynn E
LE
Luckman
Simon M
SM
D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004361:Drug Tolerance; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D007028:Hypothalamic Hormones / Q000494:pharmacology*; D007473:Ion Channels; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins; D009479:Neuropeptides / Q000494:pharmacology*; D056690:Prolactin-Releasing Hormone; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000502:physiology; D000071256:Uncoupling Protein 1; D015430:Weight Gain / Q000187:drug effects
D001067:Appetite Depressants; D002352:Carrier Proteins; D007028:Hypothalamic Hormones; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009479:Neuropeptides; C534379:Prlh protein, rat; D056690:Prolactin-Releasing Hormone; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1