title: Leptin responsiveness in mice that ectopically express agouti protein.
abstract: Agouti protein is an endogenous antagonist of melanocortin receptors (MCR), including MCR3 and MCR4, which have been implicated as part of the hypothalamic mechanism that mediates leptin-induced hypophagia. In this experiment we examined the effects of peripheral and central leptin administration in male and female beta-actin promoter (BAPa) mice that express agouti protein ectopically and have a phenotype that includes obesity and diabetes which is exaggerated in males compared with females. Intraperitoneal infusion of 10 microg leptin/day for 13 days caused weight loss and a transient inhibition of food intake in wild-type mice, with a greater effect in males than females. Male BAPa mice were resistant to leptin infusion whereas female mice lost weight. All of the mice lost body weight following a single intracerebroventricular injection of leptin but the effect was greater in female BAPa mice than any other group. There also was a delayed suppression of food intake that was the same for wild-type and BAPa female mice, whereas food intake recovered faster in BAPa than wild-type males. The dissociation between food intake and body weight loss implies a significant effect of leptin on energy expenditure in BAPa mice. These results demonstrate that the effect of leptin on energy balance is not entirely dependent upon the melanocortin system.
authors.affiliation: Department of Foods and Nutrition, University of Georgia, Dawson Hall, Athens, GA 30605, USA. harrisrb@arches.uga.edu
authors.forename: Ruth B S
authors.initials: RB
authors.lastname: Harris
authors.forename: Tiffany D
authors.initials: TD
authors.lastname: Mitchell
authors.forename: Randall L
authors.initials: RL
authors.lastname: Mynatt
mesh_terms: D054366:Agouti Signaling Protein; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000235:genetics / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000235:genetics / Q000502:physiology; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D005260:Female; D005838:Genotype; D007263:Infusions, Parenteral; D007276:Injections, Intraventricular; D007328:Insulin / Q000097:blood; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012727:Sex Characteristics
chemical_list: D054366:Agouti Signaling Protein; D001786:Blood Glucose; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D011506:Proteins; C515183:a protein, mouse