| Autor: |
Lau, Patrick, Tuong, Zewen K., Shu-Ching Wang, Fitzsimmons, Rebecca L., Goode, Joel M., Thomas, Gethin P., Cowin, Gary J., Pearen, Michael A., Mardon, Karine, Stow, Jennifer L., Muscat, George E. O. |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Endocrinology & Metabolism; 1/15/2015, Vol. 308 Issue 2, pE159-E171, 13p |
| Abstrakt: |
The Rar-related orphan receptor-α (Rorα) is a nuclear receptor that regulates adiposity and is a potential regulator of energy homeostasis. We have demonstrated that the Rorα-deficient staggerer (sg/sg) mice display a lean and obesity-resistant phenotype. Adaptive Ucp1-dependent thermogenesis in beige/brite and brown adipose tissue serves as a mechanism to increase energy expenditure and resist obesity. DEXA and MRI analysis demonstrated significantly decreased total fat mass and fat/lean mass tissue ratio in male chow-fed sg/sg mice relative to wt mice. In addition, we observed increased Ucp1 expression in brown adipose and subcutaneous white adipose tissue but not in visceral adipose tissue from Rorα-deficient mice. Moreover, this was associated with significant increases in the expression of the mRNAs encoding the thermogenic genes (i.e., markers of brown and beige adipose) Pparα, Errα, Dio2, Acot11/Bfit, Cpt1β, and Cidea in the subcutaneous adipose in the sg/sg relative to WT mice. These changes in thermogenic gene expression involved the significantly increased expression of the (cell-fate controlling) histone-lysine N-methyltransferase 1 (Ehmt1), which stabilizes the Prdm16 transcriptional complex. Moreover, primary brown adipocytes from sg/sg mice displayed a higher metabolic rate, and further analysis was consistent with increased uncoupling. Finally, core body temperature analysis and infrared thermography demonstrated that the sg/sg mice maintained greater thermal control and cold tolerance relative to the WT littermates. We suggest that enhanced Ucp1 and thermogenic gene expression/ activity may be an important contributor to the lean, obesity-resistant phenotype in Rorα-deficient mice. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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