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

Abstract

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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  • Authors+Show Affiliations

    ,

    Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.

    , , , , , , , , , ,

    Source

    Cell 120:2 2005 Jan 28 pg 261-73

    MeSH

    Animals
    CCAAT-Enhancer-Binding Proteins
    Cholesterol
    DNA-Binding Proteins
    Dietary Fats
    Gene Expression Profiling
    Gene Expression Regulation
    Hyperlipidemias
    Liver
    Liver X Receptors
    Male
    Mice
    Orphan Nuclear Receptors
    Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
    Receptors, Cytoplasmic and Nuclear
    Sterol Regulatory Element Binding Protein 1
    Trans-Activators
    Transcription Factors

    Pub Type(s)

    Journal Article
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    15680331

    Citation

    Lin, Jiandie, et al. "Hyperlipidemic Effects of Dietary Saturated Fats Mediated Through PGC-1beta Coactivation of SREBP." Cell, vol. 120, no. 2, 2005, pp. 261-73.
    Lin J, Yang R, Tarr PT, et al. Hyperlipidemic effects of dietary saturated fats mediated through PGC-1beta coactivation of SREBP. Cell. 2005;120(2):261-73.
    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), pp. 261-73.
    Lin J, et al. Hyperlipidemic Effects of Dietary Saturated Fats Mediated Through PGC-1beta Coactivation of SREBP. Cell. 2005 Jan 28;120(2):261-73. PubMed PMID: 15680331.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Hyperlipidemic effects of dietary saturated fats mediated through PGC-1beta coactivation of SREBP. AU - Lin,Jiandie, AU - Yang,Ruojing, AU - Tarr,Paul T, AU - Wu,Pei-Hsuan, AU - Handschin,Christoph, AU - Li,Siming, AU - Yang,Wenli, AU - Pei,Liming, AU - Uldry,Marc, AU - Tontonoz,Peter, AU - Newgard,Christopher B, AU - Spiegelman,Bruce M, PY - 2004/06/13/received PY - 2004/11/15/revised PY - 2004/11/22/accepted PY - 2005/2/1/pubmed PY - 2005/3/10/medline PY - 2005/2/1/entrez SP - 261 EP - 73 JF - Cell JO - Cell VL - 120 IS - 2 N2 - 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. SN - 0092-8674 UR - https://www.unboundmedicine.com/medline/citation/15680331/full_citation L2 - https://linkinghub.elsevier.com/retrieve/pii/S009286740401147X DB - PRIME DP - Unbound Medicine ER -