TR4 promotes fatty acid synthesis in 3T3-L1 adipocytes by activation of pyruvate carboxylase expression

FEBS Lett. 2014 Nov 3;588(21):3947-53. doi: 10.1016/j.febslet.2014.09.007. Epub 2014 Sep 19.

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.

Keywords: Adipocyte; Fatty acid synthesis; Pyruvate carboxylase; Testicular orphan nuclear receptor 4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism*
  • Animals
  • Fatty Acids / biosynthesis*
  • Gene Expression Regulation, Enzymologic*
  • Gene Knockdown Techniques
  • Lipogenesis
  • Mice
  • Promoter Regions, Genetic / genetics
  • Pyruvate Carboxylase / genetics*
  • Receptors, Steroid / deficiency
  • Receptors, Steroid / genetics
  • Receptors, Steroid / metabolism*
  • Receptors, Thyroid Hormone / deficiency
  • Receptors, Thyroid Hormone / genetics
  • Receptors, Thyroid Hormone / metabolism*

Substances

  • Fatty Acids
  • Nr2c2 protein, mouse
  • Receptors, Steroid
  • Receptors, Thyroid Hormone
  • Pyruvate Carboxylase