Role of adiponectin in human skeletal muscle bioenergetics

Anthony E. Civitarese, Barbara Ukropcova, Stacy Carling, Matthew Hulver, Ralph A. DeFronzo, Lawrence Mandarino, Eric Ravussin, Steve R. Smith

    Research output: Contribution to journalArticle

    175 Citations (Scopus)

    Abstract

    Insulin resistance is associated with impaired skeletal muscle oxidation capacity and reduced mitochondrial number and function. Here, we report that adiponectin signaling regulates mitochondrial bioenergetics in skeletal muscle. Individuals with a family history of type 2 diabetes display skeletal muscle insulin resistance and mitochondrial dysfunction; adiponectin levels strongly correlate with mtDNA content. Knockout of the adiponectin gene in mice is associated with insulin resistance and low mitochondrial content and reduced mitochondrial enzyme activity in skeletal muscle. Adiponectin treatment of human myotubes in primary culture induces mitochondrial biogenesis, palmitate oxidation, and citrate synthase activity, and reduces the production of reactive oxygen species. The inhibition of adiponectin receptor expression by siRNA, or of AMPK by a pharmacological agent, blunts adiponectin induction of mitochondrial function. Our findings define a skeletal muscle pathway by which adiponectin increases mitochondrial number and function and exerts antidiabetic effects.

    Original languageEnglish (US)
    Pages (from-to)75-87
    Number of pages13
    JournalCell Metabolism
    Volume4
    Issue number1
    DOIs
    StatePublished - Jul 2006

    Fingerprint

    Adiponectin
    Energy Metabolism
    Skeletal Muscle
    Insulin Resistance
    Adiponectin Receptors
    Citrate (si)-Synthase
    Gene Knockout Techniques
    AMP-Activated Protein Kinases
    Palmitates
    Skeletal Muscle Fibers
    Organelle Biogenesis
    Mitochondrial DNA
    Hypoglycemic Agents
    Type 2 Diabetes Mellitus
    Small Interfering RNA
    Reactive Oxygen Species
    human ADIPOQ protein
    Pharmacology
    Enzymes

    Keywords

    • HUMDISEASE
    • SIGNALING

    ASJC Scopus subject areas

    • Cell Biology
    • Molecular Biology
    • Physiology

    Cite this

    Civitarese, A. E., Ukropcova, B., Carling, S., Hulver, M., DeFronzo, R. A., Mandarino, L., ... Smith, S. R. (2006). Role of adiponectin in human skeletal muscle bioenergetics. Cell Metabolism, 4(1), 75-87. https://doi.org/10.1016/j.cmet.2006.05.002

    Role of adiponectin in human skeletal muscle bioenergetics. / Civitarese, Anthony E.; Ukropcova, Barbara; Carling, Stacy; Hulver, Matthew; DeFronzo, Ralph A.; Mandarino, Lawrence; Ravussin, Eric; Smith, Steve R.

    In: Cell Metabolism, Vol. 4, No. 1, 07.2006, p. 75-87.

    Research output: Contribution to journalArticle

    Civitarese, AE, Ukropcova, B, Carling, S, Hulver, M, DeFronzo, RA, Mandarino, L, Ravussin, E & Smith, SR 2006, 'Role of adiponectin in human skeletal muscle bioenergetics', Cell Metabolism, vol. 4, no. 1, pp. 75-87. https://doi.org/10.1016/j.cmet.2006.05.002
    Civitarese AE, Ukropcova B, Carling S, Hulver M, DeFronzo RA, Mandarino L et al. Role of adiponectin in human skeletal muscle bioenergetics. Cell Metabolism. 2006 Jul;4(1):75-87. https://doi.org/10.1016/j.cmet.2006.05.002
    Civitarese, Anthony E. ; Ukropcova, Barbara ; Carling, Stacy ; Hulver, Matthew ; DeFronzo, Ralph A. ; Mandarino, Lawrence ; Ravussin, Eric ; Smith, Steve R. / Role of adiponectin in human skeletal muscle bioenergetics. In: Cell Metabolism. 2006 ; Vol. 4, No. 1. pp. 75-87.
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