title: 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.
authors.affiliation: School of Kinesiology and Health Studies, Queen's University, Kingston, Ontario, Canada.
authors.forename: Cameron B
authors.initials: CB
authors.lastname: Williams
authors.affiliation: School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada.
authors.forename: Meghan C
authors.initials: MC
authors.lastname: Hughes
authors.affiliation: School of Kinesiology and Health Studies, Queen's University, Kingston, Ontario, Canada.
authors.forename: Brittany A
authors.initials: BA
authors.lastname: Edgett
authors.affiliation: School of Kinesiology and Health Studies, Queen's University, Kingston, Ontario, Canada.
authors.forename: Trisha D
authors.initials: TD
authors.lastname: Scribbans
authors.affiliation: Department of Emergency Medicine, Queen's University, Kingston, Ontario, Canada.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Simpson
authors.affiliation: School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada.
authors.forename: Christopher G R
authors.initials: CG
authors.lastname: Perry
authors.affiliation: School of Kinesiology and Health Studies, Queen's University, Kingston, Ontario, Canada.
authors.forename: Brendon J
authors.initials: BJ
authors.lastname: Gurd
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000107:Acetylation; D000273:Adipose Tissue / Q000187:drug effects; D000328:Adult; D001786:Blood Glucose; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005990:Glycerol / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000378:metabolism; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D013267:Stilbenes; D055372:AMP-Activated Protein Kinases; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D005990:Glycerol; D000077185:Resveratrol