A 35 amino acid fragment of leptin inhibits feeding in the rat

Peptide fragments of the larger 167 amino acid obesity gene related peptide (OBGRP), leptin, were tested for their ability to inhibit feeding in the rat. The C-terminal fragment, OBGRP 116-167 exerted only minimal inhibition of feeding when administered into the lateral cerebroventricle. No alteration in feeding was observed following administration of OBGRP 57-92. We hypothesized that the satiety effects of leptin reside in the N-terminal region of the peptide sequence. Significant, dose-related, and reversible inhibition of food intake was observed following central administration of the 35 amino acid fragment OBGRP 22-56. These results suggest that a small, readily synthesized fragment of the 167 amino acid peptide leptin may exert physiologically relevant satiety effects in brain revealing an endocrine feedback mechanism by which the adipocyte may modulate hypothalamic function.