Strain-Dependent Stimulation of Growth in Leptin-Treated Obesedb/dbMice

Abram M. Madiehe, Sadie Hebert, Tiffany D. Mitchell, Ruth B. S. Harris
2002 Endocrinology  
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 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.
more » ... sed C57BL/6J db/db mice gained more weight (ϳ20%; 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. (Endocrinology 143: 3875-3883, 2002) Abbreviations: FFA, Free fatty acids; JAK, Janus-activated kinase; OGTT, oral glucose tolerance test.
doi:10.1210/en.2002-220362 pmid:12239099 fatcat:6acgnpwsire3bhjshgza3w2ymm