SREBP-1-independent regulation of lipogenic gene expression in adipocytes

J Lipid Res. 2007 Jul;48(7):1581-91. doi: 10.1194/jlr.M700033-JLR200. Epub 2007 Apr 24.

Abstract

Sterol regulatory element-binding protein (SREBP)-1c is now well established as a key transcription factor for the regulation of lipogenic enzyme genes such as FAS in hepatocytes. Meanwhile, the mechanisms of lipogenic gene regulation in adipocytes remain unclear. Here, we demonstrate that those in adipocytes are independent of SREBP-1c. In adipocytes, unlike in hepatocytes, the stimulation of SREBP-1c expression by liver X receptor agonist does not accompany lipogenic gene upregulation, although nuclear SREBP-1c protein is concomitantly increased, indicating that the activation process of SREBP-1c by the cleavage system is intact in adipocytes. Supportively, transcriptional activity of the mature form of SREBP-1c for the FAS promoter was negligible when measured by reporter analysis. As an underlying mechanism, accessibility of SREBP-1c to the functional elements was involved, because chromatin immunoprecipitation assays revealed that SREBP-1c does not bind to the functional SRE/E-box site on the FAS promoter in adipocytes. Moreover, genetic disruption of SREBP-1 did not cause any changes in lipogenic gene expression in adipose tissue. In summary, in adipocytes, unlike in hepatocytes, increments in nuclear SREBP-1c are not accompanied by transactivation of lipogenic genes; thus, SREBP-1c is not committed to the regulation of lipogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / physiology*
  • Animals
  • Cells, Cultured
  • DNA-Binding Proteins / agonists
  • DNA-Binding Proteins / physiology
  • Fatty Acid Synthases / metabolism
  • Gene Expression Regulation / physiology*
  • Hepatocytes / physiology
  • Hydrocarbons, Fluorinated
  • Liver X Receptors
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Orphan Nuclear Receptors
  • Protein Processing, Post-Translational
  • Rats
  • Rats, Wistar
  • Receptors, Cytoplasmic and Nuclear / agonists
  • Receptors, Cytoplasmic and Nuclear / physiology
  • Sterol Regulatory Element Binding Protein 1 / physiology*
  • Sulfonamides

Substances

  • DNA-Binding Proteins
  • Hydrocarbons, Fluorinated
  • Liver X Receptors
  • Orphan Nuclear Receptors
  • Receptors, Cytoplasmic and Nuclear
  • Srebf1 protein, mouse
  • Sterol Regulatory Element Binding Protein 1
  • Sulfonamides
  • T0901317
  • Fatty Acid Synthases