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.
Highlights
Resveratrol (RSV), a plant derived polyphenol, has recently garnered significant interest due to its purported beneficial effects on glucose homeostasis and metabolic health [1]
The specific actions of RSV are further complicated by evidence that RSV activates AMPK in muscle [16,17] and adipose tissue [17] and findings that the activation of AMPK is required for the beneficial effects of RSV to manifest [17]
While there was a significant effect of time (P,0.05) observed for p-PKA substrates between 50 and 250 kDa, no effects of time or RSV were observed for the acetylation status of p53 (SIRT1 substrate), p-AMPK or p-ACC (Fig. 1B)
Summary
Resveratrol (RSV), a plant derived polyphenol, has recently garnered significant interest due to its purported beneficial effects on glucose homeostasis and metabolic health [1]. The specific actions of RSV are further complicated by evidence that RSV activates AMPK in muscle [16,17] and adipose tissue [17] and findings that the activation of AMPK is required for the beneficial effects of RSV to manifest [17]. These findings have led to the speculation that RSV activates both SIRT1 and AMPK with direct activation of SIRT1 stimulating AMPK activity via LKB1 [18] or indirect activation of SIRT occurring via AMPK subsequent to an effect of RSV on PDE/cAMP signalling [19]. While there is evidence that this effect may be dose dependent [18], and impaired ATP production has yet to be demonstrated in vivo, the idea that RSV mediated activation of AMPK results from a disturbance in energy status is compelling
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
