Peptide S is a novel potent inhibitor of voluntary and fast-induced food intake in rats.
Peptide S (NPS or PEPS) and its cognate receptor have been recently identified both in the central nervous system and in the periphery. NPS/PEPS promotes arousal and has potent anxiolytic-like effects when it is injected centrally in mice. In the present experiment, we tested by different approaches its central effects on feeding behaviour in Long-Evans rats. PEPS at doses of 1 and 10 microg injected in the lateral brain ventricle strongly inhibited by more than 50% chow intake in overnight fasted rats with effects of longer duration with the highest dose (P<0.0001). A similar decrease was observed for the spontaneous intake of a high-energy palatable diet (-48%; P<0.0001). This anorexigenic effect was comparable to that induced by corticotropin-releasing hormone in fasted rats at equimolar doses. However, peptide S did not modify food intake stimulated by neuropeptide Y (NPY) at equimolar doses. It also did not affect the fasting concentrations of important modulators of food intake like leptin, ghrelin, and insulin in circulation. This study therefore showed that peptide S is a new potent anorexigenic agent when centrally injected. Its inhibitory action appears to be independent of the NPY, ghrelin, and leptin pathways. Development of peptide S agonists could constitute a new approach for the treatment of obesity.
Beck
Bernard
B
University Henri Poincaré, Neurocal, 38 rue Lionnois, 54000 Nancy, France. Bernard.Beck@nancy.inserm.fr
Fernette
Brigitte
B
Stricker-Krongrad
Alain
A
D000818:Animals; D001067:Appetite Depressants / Q000008:administration & dosage / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D005215:Fasting; D006728:Hormones / Q000097:blood; D007276:Injections, Intraventricular; D008297:Male; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D009478:Neuropeptide Y / Q000008:administration & dosage; D051381:Rats; D020318:Rats, Long-Evans
D001067:Appetite Depressants; D006728:Hormones; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D003346:Corticotropin-Releasing Hormone