Abnormal protein turnover and anabolic resistance to exercise in sarcopenic obesity

FASEB J. 2013 Oct;27(10):3905-16. doi: 10.1096/fj.12-224006. Epub 2013 Jun 26.

Abstract

Obesity may impair protein synthesis rates and cause anabolic resistance to growth factors, hormones, and exercise, ultimately affecting skeletal muscle mass and function. To better understand muscle wasting and anabolic resistance with obesity, we assessed protein 24-h fractional synthesis rates (24-h FSRs) in selected hind-limb muscles of sedentary and resistance-exercised lean and obese Zucker rats. Despite atrophied hind-limb muscles (-28% vs. lean rats), 24-h FSRs of mixed proteins were significantly higher in quadriceps (+18%) and red or white gastrocnemius (+22 or +38%, respectively) of obese animals when compared to lean littermates. Basal synthesis rates of myofibrillar (+8%) and mitochondrial proteins (-1%) in quadriceps were not different between phenotypes, while manufacture of cytosolic proteins (+12%) was moderately elevated in obese cohorts. Western blot analyses revealed a robust activation of p70S6k (+178%) and a lower expression of the endogenous mTOR inhibitor DEPTOR (-28%) in obese rats, collectively suggesting that there is an obesity-induced increase in net protein turnover favoring degradation. Lastly, the protein synthetic response to exercise of mixed (-7%), myofibrillar (+6%), and cytosolic (+7%) quadriceps subfractions was blunted compared to the lean phenotype (+34, +40, and +17%, respectively), indicating a muscle- and subfraction-specific desensitization to the anabolic stimulus of exercise in obese animals.

Keywords: DEPTOR; diabetes; fractional synthesis rates; muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation / physiology
  • Male
  • Obesity / metabolism*
  • Physical Conditioning, Animal / physiology*
  • Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Zucker
  • Ribosomal Protein S6 Kinases, 70-kDa / genetics
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • Sarcopenia / metabolism*
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Proteins
  • TOR Serine-Threonine Kinases
  • mTOR protein, rat
  • Proto-Oncogene Proteins c-akt
  • Ribosomal Protein S6 Kinases, 70-kDa