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

Publication ,  Journal Article
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 in: Cell
January 28, 2005

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.

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Published In

Cell

DOI

ISSN

0092-8674

Publication Date

January 28, 2005

Volume

120

Issue

2

Start / End Page

261 / 273

Location

United States

Related Subject Headings

  • Transcription Factors
  • Trans-Activators
  • Sterol Regulatory Element Binding Protein 1
  • Receptors, Cytoplasmic and Nuclear
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Orphan Nuclear Receptors
  • Mice
  • Male
  • Liver X Receptors
  • Liver
 

Citation

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Lin, J., Yang, R., Tarr, P. T., Wu, P.-H., Handschin, C., Li, S., … Spiegelman, B. M. (2005). Hyperlipidemic effects of dietary saturated fats mediated through PGC-1beta coactivation of SREBP. Cell, 120(2), 261–273. https://doi.org/10.1016/j.cell.2004.11.043
Lin, Jiandie, Ruojing Yang, Paul T. Tarr, Pei-Hsuan Wu, Christoph Handschin, Siming Li, Wenli Yang, et al. “Hyperlipidemic effects of dietary saturated fats mediated through PGC-1beta coactivation of SREBP.Cell 120, no. 2 (January 28, 2005): 261–73. https://doi.org/10.1016/j.cell.2004.11.043.
Lin J, Yang R, Tarr PT, Wu P-H, Handschin C, Li S, et al. Hyperlipidemic effects of dietary saturated fats mediated through PGC-1beta coactivation of SREBP. Cell. 2005 Jan 28;120(2):261–73.
Lin, Jiandie, et al. “Hyperlipidemic effects of dietary saturated fats mediated through PGC-1beta coactivation of SREBP.Cell, vol. 120, no. 2, Jan. 2005, pp. 261–73. Pubmed, doi:10.1016/j.cell.2004.11.043.
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. Hyperlipidemic effects of dietary saturated fats mediated through PGC-1beta coactivation of SREBP. Cell. 2005 Jan 28;120(2):261–273.
Journal cover image

Published In

Cell

DOI

ISSN

0092-8674

Publication Date

January 28, 2005

Volume

120

Issue

2

Start / End Page

261 / 273

Location

United States

Related Subject Headings

  • Transcription Factors
  • Trans-Activators
  • Sterol Regulatory Element Binding Protein 1
  • Receptors, Cytoplasmic and Nuclear
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Orphan Nuclear Receptors
  • Mice
  • Male
  • Liver X Receptors
  • Liver