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 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.
Grasso
P
P
Department of Biochemistry and Molecular Biology, Albany Medical College, New York 12208, USA. pgrasso@ccgateway.amc.edu
White
D W
DW
Tartaglia
L A
LA
Leinung
M C
MC
Lee
D W
DW
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D001833:Body Temperature Regulation / Q000187:drug effects; D019556:COS Cells; D002352:Carrier Proteins / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D005247:Feeding Behavior / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006720:Homozygote; D007031:Hypothalamus / Q000502:physiology; D020738:Leptin / Q000494:pharmacology*; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D010446:Peptide Fragments / Q000494:pharmacology*; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D014162:Transfection; D015430:Weight Gain / Q000187:drug effects* / Q000502:physiology
D001786:Blood Glucose; D002352:Carrier Proteins; D020738:Leptin; D008024:Ligands; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011994:Recombinant Proteins; C515447:leptin receptor, mouse