title: Testosterone interacts with the feedback mechanisms engaged by Tyr985 of the leptin receptor and diet-induced obesity.
abstract: Inhibitory signaling through Tyr985 of the leptin receptor contributes to the attenuation of anorectic leptin action in obese animals. Leptin receptor (LEPR-B) Tyr985Leu homozygote mutant mice (termed l/l) were previously generated to study Tyr985's contributions to inhibition of LEPR-B signaling; young female l/l mice display a lean, leptin-sensitive phenotype, while young male l/l are not significantly different from wild-type. We report here that testosterone (but not estrogen) determines the sex-specificity of the l/l phenotype. This provides additional insight into the cellular mechanism by which gonadal hormones determine central sensitivity to leptin, and may help elucidate the long-noted sex differences in leptin sensitivity. Additionally, we observed that Tyr985 signaling protects against a diet-dependent switch that exacerbates obesity with high fat feeding, such that the enhanced leptin sensitivity of l/l mice on a normal diet leads to increased adiposity in the face of chronic high-fat diet.
authors: School of Kinesiology, University of Michigan, 3730 Central Campus Recreational Building, 401 Washtenaw Avenue, Ann Arbor, MI 48109, USA. uniqenam@umich.edu
authors: Joshua A
authors: JA
authors: Johnson
authors: Sal
authors: S
authors: Calo
authors: Lekshmi
authors: L
authors: Nair
authors: Heidi B
authors: HB
authors: IglayReger
authors: Megan
authors: M
authors: Greenwald-Yarnell
authors: Josh
authors: J
authors: Skorupski
authors: Martin G
authors: MG
authors: Myers
authors: Peter F
authors: PF
authors: Bodary
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D025461:Feedback, Physiological; D005260:Female; D007031:Hypothalamus / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D009919:Orchiectomy; D010052:Ovariectomy; D011944:Receptors, Androgen / Q000378:metabolism; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism* / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D011944:Receptors, Androgen; D054411:Receptors, Leptin; C515447:leptin receptor, mouse; D013739:Testosterone; D014443:Tyrosine; D004958:Estradiol