Strain-dependent stimulation of growth in leptin-treated obese db/db mice.
Leptin increases the proliferation of various cell types in vitro, and we reported that background strain influences the metabolic responses to leptin in db/db mice, which express short-form, but not long-form, leptin receptors. Here, we examined the effects of leptin on growth of young C57BL/Ks, C57BL/6J, and C57BL/3J db/db mice. Intraperitoneal infusions of 20 micro g leptin/d for 26 d increased the food intake of C57BL/6J mice by 15% (P < 0.01), but had no effect in C57BL/Ks db/db mice. Leptin-infused C57BL/6J db/db mice gained more weight ( approximately 20%; P < 0.04) than PBS-infused controls. The increased weight was sustained after leptin infusion ended. Leptin had no effect on weight gain or food intake of C57BL/3J db/db mice, which only express the soluble leptin receptor. A single leptin injection increased MAPK phosphorylation in liver by 40% (P < 0.001) and that in muscle tissues by 20% (P < 0.001) in C57BL/6J mice, but did not change phosphorylation in C57BL/3J db/db mice. These results suggest that leptin increases the weight gain of C57BL/6J db/db mice by activating the MAPK pathway through a mechanism that is dependent on short-form leptin receptors. This response may be masked by activation of the long-form receptor in wild-type animals that lose body fat during leptin treatment.
Madiehe
Abram M
AM
Department of Foods and Nutrition, University of Georgia, Athens 30602, USA. madiehe@arches.uga.edu
Hebert
Sadie
S
Mitchell
Tiffany D
TD
Harris
Ruth B S
RB
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D003920:Diabetes Mellitus / Q000235:genetics / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D007263:Infusions, Parenteral; D020738:Leptin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009765:Obesity; D013045:Species Specificity
D020738:Leptin; D020928:Mitogen-Activated Protein Kinases