Inhibitory effects of leptin-related synthetic peptide 116-130 on food intake and body weight gain in female C57BL/6J ob/ob mice may not be mediated by peptide activation of the long isoform of the leptin receptor

We recently reported that intraperitoneal administration of leptin-related synthetic peptide 116-130 [LEP-(116-130)] resulted in reduced food intake a nd significant weight loss in homozygous female C57BL/6J ob/ob mice. In thi s study, we used two in vitro bioassays to show that the interaction of LEP -(116-130) with the long form of the leptin receptor (OB-R-b), the receptor isoform that is predominantly expressed in the hypothalamus, is not requir ed for the observed in vivo effects of the peptide on energy balance. LEP-( 116-130) was unable to compete the binding of alkaline phosphatase-leptin f usion protein to OB-R. Moreover, LEP-(116-130) was unable to activate signa l transduction by OB-R-b in vitro. In homozygous female C57BLKS/J-m db/db m ice that do not express OB-R-b, intraperitoneal administration of LEP-(116- 130) reduced body weight gain and blood glucose levels but not food intake, which further supports a mechanism of action that does not require peptide interaction with OB-R-b.