Testosterone interacts with the feedback mechanisms engaged by Tyr985 of the leptin receptor and diet-induced obesity
| Autor: | Lekshmi Nair, Heidi B. IglayReger, Megan Greenwald-Yarnell, Peter F. Bodary, Sal Calo, Martin G. Myers, Joshua A. Johnson, Josh Skorupski |
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| Rok vydání: | 2012 |
| Předmět: |
Male
medicine.medical_specialty Normal diet medicine.drug_class Ovariectomy Endocrinology Diabetes and Metabolism Clinical Biochemistry Hypothalamus Biology Diet High-Fat Biochemistry Mice Endocrinology Internal medicine medicine Animals Testosterone Longitudinal Studies Obesity Receptor Molecular Biology Feedback Physiological Mice Knockout Leptin receptor Estradiol Leptin digestive oral and skin physiology Cell Biology Receptors Androgen Estrogen LDL receptor Anorectic Receptors Leptin Tyrosine Molecular Medicine Female Orchiectomy hormones hormone substitutes and hormone antagonists |
| Zdroj: | The Journal of Steroid Biochemistry and Molecular Biology. 132:212-219 |
| ISSN: | 0960-0760 |
| DOI: | 10.1016/j.jsbmb.2012.06.002 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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