Hyperlipidemic effects of dietary saturated fats mediated through PGC-1beta coactivation of SREBP.

Published

Journal Article

The PGC-1 family of coactivators stimulates the activity of certain transcription factors and nuclear receptors. Transcription factors in the sterol responsive element binding protein (SREBP) family are key regulators of the lipogenic genes in the liver. We show here that high-fat feeding, which induces hyperlipidemia and atherogenesis, stimulates the expression of both PGC-1beta and SREBP1c and 1a in liver. PGC-1beta coactivates the SREBP transcription factor family and stimulates lipogenic gene expression. Further, PGC-1beta is required for SREBP-mediated lipogenic gene expression. However, unlike SREBP itself, PGC-1beta reduces fat accumulation in the liver while greatly increasing circulating triglycerides and cholesterol in VLDL particles. The stimulation of lipoprotein transport upon PGC-1beta expression is likely due to the simultaneous coactivation of the liver X receptor, LXRalpha, a nuclear hormone receptor with known roles in hepatic lipid transport. These data suggest a mechanism through which dietary saturated fats can stimulate hyperlipidemia and atherogenesis.

Full Text

Duke Authors

Cited Authors

  • Lin, J; Yang, R; Tarr, PT; Wu, P-H; Handschin, C; Li, S; Yang, W; Pei, L; Uldry, M; Tontonoz, P; Newgard, CB; Spiegelman, BM

Published Date

  • January 28, 2005

Published In

Volume / Issue

  • 120 / 2

Start / End Page

  • 261 - 273

PubMed ID

  • 15680331

Pubmed Central ID

  • 15680331

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2004.11.043

Language

  • eng

Conference Location

  • United States