Resveratrol prevents sarcopenic obesity by reversing mitochondrial dysfunction and oxidative stress via the PKA/LKB1/AMPK pathway

Aging (Albany NY). 2019 Apr 15;11(8):2217-2240. doi: 10.18632/aging.101910.

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.

Keywords: AMPK; mitochondrial function; oxidative stress; resveratrol; sarcopenic obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • Adenylate Kinase / metabolism
  • Aging / metabolism
  • Animals
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Diet, High-Fat / adverse effects
  • Male
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / metabolism
  • Muscular Atrophy / drug therapy
  • Muscular Atrophy / metabolism
  • Obesity / etiology
  • Obesity / metabolism
  • Obesity / prevention & control*
  • Oxidative Stress / drug effects*
  • Palmitic Acid / pharmacology
  • Protein Serine-Threonine Kinases / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Resveratrol / pharmacology*
  • Resveratrol / therapeutic use
  • Sarcopenia / etiology
  • Sarcopenia / metabolism
  • Sarcopenia / prevention & control*
  • Signal Transduction / drug effects*

Substances

  • Antioxidants
  • Palmitic Acid
  • Protein Serine-Threonine Kinases
  • Stk11 protein, rat
  • Cyclic AMP-Dependent Protein Kinases
  • AMP-Activated Protein Kinase Kinases
  • Adenylate Kinase
  • Resveratrol