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.

Abstract	We recently reported that intraperitoneal administration of leptin-related synthetic peptide 116-130 [LEP-(116-130)] resulted in reduced food intake and significant weight loss in homozygous female C57BL/6J ob/ob mice. In this 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-Rb), the receptor isoform that is predominantly expressed in the hypothalamus, is not required 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 fusion protein to OB-R. Moreover, LEP-(116-130) was unable to activate signal transduction by OB-Rb in vitro. In homozygous female C57BLKS/J-m db/db mice that do not express OB-Rb, 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-Rb.
Authors	P Grasso, D W White, L A Tartaglia, M C Leinung, D W Lee
Journal	Diabetes (Diabetes) Vol. 48 Issue 11 Pg. 2204-9 (Nov 1999) ISSN: 0012-1797 [Print] United States
PMID	10535455 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Blood Glucose Carrier Proteins Leptin Ligands Peptide Fragments Receptors, Cell Surface Receptors, Leptin Recombinant Proteins leptin receptor, mouse
Topics	Animals Blood Glucose (drug effects, metabolism) Body Temperature Regulation (drug effects) COS Cells Carrier Proteins (drug effects, genetics, physiology) Cell Line Feeding Behavior (drug effects, physiology) Female Homozygote Hypothalamus (physiology) Leptin (pharmacology) Ligands Mice Mice, Inbred C57BL Mice, Obese Peptide Fragments (pharmacology) Receptors, Cell Surface Receptors, Leptin Recombinant Proteins (drug effects, metabolism) Transfection Weight Gain (drug effects, physiology)

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