Repeated administration of the anorectic factor prolactin-releasing peptide leads to tolerance to its effects on energy homeostasis.

Ellacott KL, Lawrence CB, Pritchard LE, Luckman SM
Am J Physiol Regul Integr Comp Physiol. 2003 285 (5): R1005-10

PMID: 14557233 · DOI:10.1152/ajpregu.00237.2003

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.

MeSH Terms (21)

Adipose Tissue, Brown Animals Appetite Depressants Carrier Proteins Drug Tolerance Eating Energy Metabolism Gene Expression Homeostasis Hypothalamic Hormones Ion Channels Male Membrane Proteins Mitochondrial Proteins Neuropeptides Prolactin-Releasing Hormone Rats Rats, Sprague-Dawley Sympathetic Nervous System Uncoupling Protein 1 Weight Gain

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