Resveratrol Improves Mitochondrial Function and Protects against Metabolic Disease by Activating SIRT1 and PGC-1α

Marie Lagouge, Carmen Argmann, Zachary Gerhart-Hines, Hamid Meziane, Carles Lerin, Frederic Daussin, Nadia Messadeq, Jill Milne, Philip Lambert, Peter Elliott, Bernard Geny, Markku Laakso, Pere Puigserver, Johan Auwerx

    Research output: Contribution to journalArticle

    Abstract

    Diminished mitochondrial oxidative phosphorylation and aerobic capacity are associated with reduced longevity. We tested whether resveratrol (RSV), which is known to extend lifespan, impacts mitochondrial function and metabolic homeostasis. Treatment of mice with RSV significantly increased their aerobic capacity, as evidenced by their increased running time and consumption of oxygen in muscle fibers. RSV's effects were associated with an induction of genes for oxidative phosphorylation and mitochondrial biogenesis and were largely explained by an RSV-mediated decrease in PGC-1α acetylation and an increase in PGC-1α activity. This mechanism is consistent with RSV being a known activator of the protein deacetylase, SIRT1, and by the lack of effect of RSV in SIRT1-/- MEFs. Importantly, RSV treatment protected mice against diet-induced-obesity and insulin resistance. These pharmacological effects of RSV combined with the association of three Sirt1 SNPs and energy homeostasis in Finnish subjects implicates SIRT1 as a key regulator of energy and metabolic homeostasis.

    Original languageEnglish (US)
    Pages (from-to)1109-1122
    Number of pages14
    JournalCell
    Volume127
    Issue number6
    DOIs
    StatePublished - Dec 15 2006

    ASJC Scopus subject areas

    • Cell Biology
    • Molecular Biology

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  • Cite this

    Lagouge, M., Argmann, C., Gerhart-Hines, Z., Meziane, H., Lerin, C., Daussin, F., Messadeq, N., Milne, J., Lambert, P., Elliott, P., Geny, B., Laakso, M., Puigserver, P., & Auwerx, J. (2006). Resveratrol Improves Mitochondrial Function and Protects against Metabolic Disease by Activating SIRT1 and PGC-1α. Cell, 127(6), 1109-1122. https://doi.org/10.1016/j.cell.2006.11.013