title: TR4 promotes fatty acid synthesis in 3T3-L1 adipocytes by activation of pyruvate carboxylase expression.
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 (14)C from (14)C-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.
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Chonnam National University, South Korea.
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Park
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Chonnam National University, South Korea.
authors.forename: Seung-Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Chonnam National University, South Korea.
authors.forename: Hojung
authors.initials: H
authors.lastname: Choi
authors.affiliation: George Whipple Laboratory for Cancer Research, Departments of Pathology and Urology, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Chawnshang
authors.initials: C
authors.lastname: Chang
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Chonnam National University, South Korea. Electronic address: ekim@chonnam.ac.kr.
authors.forename: Eungseok
authors.initials: E
authors.lastname: Kim
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D005227:Fatty Acids / Q000096:biosynthesis*; D015971:Gene Expression Regulation, Enzymologic; D055785:Gene Knockdown Techniques; D050155:Lipogenesis; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D011766:Pyruvate Carboxylase / Q000235:genetics*; D011987:Receptors, Steroid / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; C490514:Nr2c2 protein, mouse; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D011766:Pyruvate Carboxylase
keywords: Adipocyte; Fatty acid synthesis; Pyruvate carboxylase; Testicular orphan nuclear receptor 4