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An examination of resveratrol's mechanisms of action in human tissue: impact of a single dose in vivo and dose responses in skeletal muscle ex vivo.

Abstract

The current study tested the hypothesis that a single, moderate dose of RSV would activate the AMPK/SIRT1 axis in human skeletal muscle and adipose tissue. Additionally, the effects of RSV on mitochondrial respiration in PmFBs were examined. Eight sedentary men (23.8±2.4 yrs; BMI: 32.7±7.1) reported to the lab on two occasions where they were provided a meal supplemented with 300 mg of RSV or a placebo. Blood samples, and a muscle biopsy were obtained in the fasted state and again, with the addition of an adipose tissue biopsy, two hours post-prandial. The effect of RSV on mitochondrial respiration was examined in PmFBs taken from muscle biopsies from an additional eight men (23.4±5.4 yrs; BMI: 24.4±2.8). No effect of RSV was observed on nuclear SIRT1 activity, acetylation of p53, or phosphorylation of AMPK, ACC or PKA in either skeletal muscle or adipose tissue. A decrease in post absorptive insulin levels was accompanied by elevated skeletal muscle phosphorylation of p38 MAPK, but no change in either skeletal muscle or adipose tissue insulin signalling. Mitochondrial respiration in PmFBs was rapidly inhibited by RSV at 100-300 uM depending on the substrate examined. These results question the efficacy of a single dose of RSV at altering skeletal muscle and adipose tissue AMPK/SIRT1 activity in humans and suggest that RSV mechanisms of action in humans may be associated with altered cellular energetics resulting from impaired mitochondrial ATP production.

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  • Authors+Show Affiliations

    ,

    School of Kinesiology and Health Studies, Queen's University, Kingston, Ontario, Canada.

    ,

    School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada.

    ,

    School of Kinesiology and Health Studies, Queen's University, Kingston, Ontario, Canada.

    ,

    School of Kinesiology and Health Studies, Queen's University, Kingston, Ontario, Canada.

    ,

    Department of Emergency Medicine, Queen's University, Kingston, Ontario, Canada.

    ,

    School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada.

    School of Kinesiology and Health Studies, Queen's University, Kingston, Ontario, Canada.

    Source

    PloS one 9:7 2014 pg e102406

    MeSH

    AMP-Activated Protein Kinases
    Acetylation
    Adipose Tissue
    Adult
    Blood Glucose
    Cross-Over Studies
    Double-Blind Method
    Glycerol
    Humans
    Insulin
    Male
    Mitochondria
    Muscle, Skeletal
    Resveratrol
    Signal Transduction
    Sirtuin 1
    Stilbenes

    Pub Type(s)

    Journal Article
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    25019209

    Citation

    Williams, Cameron B., et al. "An Examination of Resveratrol's Mechanisms of Action in Human Tissue: Impact of a Single Dose in Vivo and Dose Responses in Skeletal Muscle Ex Vivo." PloS One, vol. 9, no. 7, 2014, pp. e102406.
    Williams CB, Hughes MC, Edgett BA, et al. An examination of resveratrol's mechanisms of action in human tissue: impact of a single dose in vivo and dose responses in skeletal muscle ex vivo. PLoS ONE. 2014;9(7):e102406.
    Williams, C. B., Hughes, M. C., Edgett, B. A., Scribbans, T. D., Simpson, C. A., Perry, C. G., & Gurd, B. J. (2014). An examination of resveratrol's mechanisms of action in human tissue: impact of a single dose in vivo and dose responses in skeletal muscle ex vivo. PloS One, 9(7), pp. e102406. doi:10.1371/journal.pone.0102406.
    Williams CB, et al. An Examination of Resveratrol's Mechanisms of Action in Human Tissue: Impact of a Single Dose in Vivo and Dose Responses in Skeletal Muscle Ex Vivo. PLoS ONE. 2014;9(7):e102406. PubMed PMID: 25019209.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - An examination of resveratrol's mechanisms of action in human tissue: impact of a single dose in vivo and dose responses in skeletal muscle ex vivo. AU - Williams,Cameron B, AU - Hughes,Meghan C, AU - Edgett,Brittany A, AU - Scribbans,Trisha D, AU - Simpson,Craig A, AU - Perry,Christopher G R, AU - Gurd,Brendon J, Y1 - 2014/07/14/ PY - 2014/01/26/received PY - 2014/06/18/accepted PY - 2014/7/15/entrez PY - 2014/7/16/pubmed PY - 2016/1/2/medline SP - e102406 EP - e102406 JF - PloS one JO - PLoS ONE VL - 9 IS - 7 N2 - The current study tested the hypothesis that a single, moderate dose of RSV would activate the AMPK/SIRT1 axis in human skeletal muscle and adipose tissue. Additionally, the effects of RSV on mitochondrial respiration in PmFBs were examined. Eight sedentary men (23.8±2.4 yrs; BMI: 32.7±7.1) reported to the lab on two occasions where they were provided a meal supplemented with 300 mg of RSV or a placebo. Blood samples, and a muscle biopsy were obtained in the fasted state and again, with the addition of an adipose tissue biopsy, two hours post-prandial. The effect of RSV on mitochondrial respiration was examined in PmFBs taken from muscle biopsies from an additional eight men (23.4±5.4 yrs; BMI: 24.4±2.8). No effect of RSV was observed on nuclear SIRT1 activity, acetylation of p53, or phosphorylation of AMPK, ACC or PKA in either skeletal muscle or adipose tissue. A decrease in post absorptive insulin levels was accompanied by elevated skeletal muscle phosphorylation of p38 MAPK, but no change in either skeletal muscle or adipose tissue insulin signalling. Mitochondrial respiration in PmFBs was rapidly inhibited by RSV at 100-300 uM depending on the substrate examined. These results question the efficacy of a single dose of RSV at altering skeletal muscle and adipose tissue AMPK/SIRT1 activity in humans and suggest that RSV mechanisms of action in humans may be associated with altered cellular energetics resulting from impaired mitochondrial ATP production. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/25019209/full_citation L2 - http://dx.plos.org/10.1371/journal.pone.0102406 DB - PRIME DP - Unbound Medicine ER -