Research Paper Volume 11, Issue 8 pp 2217—2240
Resveratrol prevents sarcopenic obesity by reversing mitochondrial dysfunction and oxidative stress via the PKA/LKB1/AMPK pathway
- 1 Research Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Shapingba District, Chongqing 400038, P. R. China
Received: November 15, 2018 Accepted: April 4, 2019 Published: April 15, 2019
https://doi.org/10.18632/aging.101910How to Cite
Copyright: Huang et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: The concept of sarcopenic obesity refers to low muscle mass coupled with high adiposity in older adults. Sarcopenic obesity is a new medical challenge that imposes tremendous financial burdens on healthcare authorities worldwide. This study investigated the effects of resveratrol on high-fat diet-induced sarcopenic obesity in aged rats and palmitate acid-induced muscle atrophy in L6 myotubes and explored the underlying mechanisms.
Results: In vivo, resveratrol prevented muscle loss and myofiber size decrease, improved grip strength and abolished excessive fat accumulation. In vitro, resveratrol inhibited the palmitate acid-mediated reductions in myosin heavy chain content and myotube diameter. Moreover, resveratrol ameliorated mitochondrial dysfunction and oxidative stress, leading to an improvement in protein metabolism and contributing to the prevention of muscle atrophy. Furthermore, the protective effects of resveratrol on mitochondrial function, oxidative stress and muscle atrophy were abolished by PKA siRNA, LKB1 siRNA and AMPK siRNA transfection in vitro.
Conclusions: Resveratrol prevented high-fat diet-induced muscle atrophy in aged rats by reversing mitochondrial dysfunction and oxidative stress, which was partially mediated by the PKA/LKB1/AMPK pathway. These findings indicate that resveratrol might have potential uses for the prevention and treatment of sarcopenic obesity.
Abbreviations
PKA: protein kinase A; LKB1: liver kinase B1; AMPK: AMP-activated protein kinase; CD: chow diet; HFD: high fat diet; PA: palmitate acid; RSV: resveratrol; CCK-8: Cell Counting Kit-8; TG: total triglyceride; TC: total cholesterol; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; VAT: visceral adipose tissue; SAT: subcutaneous adipose tissue; IFM: intermyofibrillar mitochondria; SSM: subsarcolemmal mitochondria; TEM: transmission electron microscopy; Δψm: mitochondrial membrane potential; OCR: oxygen consumption rate; ROS: reactive oxygen species; mtROS: mitochondrial ROS; T-AOC: total antioxidative capability; SOD: superoxide dismutase; GPx: glutathione peroxidase; MDA: malonaldehyde; NAC: N-acetyl-L-cysteine; MHC: myosin heavy chain.