TR4 promotes fatty acid synthesis in 3T3-L1 adipocytes by activation of pyruvate carboxylase expression |
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| Authors: | Sung-Soo Park Seung-Jin Kim Hojung Choi Chawnshang Chang Eungseok Kim |
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| Institution: | 1. Department of Biological Sciences, College of Natural Sciences, Chonnam National University, South Korea;2. George Whipple Laboratory for Cancer Research, Departments of Pathology and Urology, University of Rochester Medical Center, Rochester, NY 14642, USA |
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| Abstract: | We show that testicular orphan nuclear receptor 4 (TR4) increases the expression of pyruvate carboxylase (PC) gene in 3T3-L1 adipocytes by direct binding to a TR4 responsive element in the murine PC promoter. While TR4 overexpression increased PC activity, oxaloacetate (OAA) and glycerol levels with enhanced incorporation of 14C from 14C-pyruvate into fatty acids in 3T3-L1 adipocytes, PC knockdown by short interfering RNA (siRNA) or inhibition of PC activity by phenylacetic acid (PAA) abolished TR4-enhanced fatty acid synthesis. Moreover, TR4 microRNA reduced PC expression with decreased fatty acid synthesis in 3T3-L1 adipocytes, suggesting that TR4-mediated enhancement of fatty acid synthesis in adipocytes requires increased expression of PC gene. |
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| Keywords: | TR4 testicular orphan nuclear receptor 4 PC pyruvate carboxylase OAA oxaloacetate PAA phenylacetic acid siRNA short interfering RNA miR microRNA FFAs free fatty acids |
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