Proteome Analysis of Skeletal Muscle From Obese and Morbidly Obese Women

  1. Dustin S. Hittel1,
  2. Yetrib Hathout1,
  3. Eric P. Hoffman1 and
  4. Joseph A. Houmard2
  1. 1Research Center for Genetic Medicine, Children’s National Medical Center, Washington, DC
  2. 2Department of Exercise and Sport Science and the Human Performance Laboratory and Diabetes/Obesity Center, East Carolina University, Greenville, North Carolina
  1. Address correspondence and reprint requests to Joseph A. Houmard, Department of Exercise and Sport Science and the Human Performance Laboratory and Diabetes/Obesity Center, East Carolina University, Greenville, NC 27858. E-mail: houmardj{at}mail.ecu.edu

Abstract

Obesity-related diseases such as the metabolic syndrome and type 2 diabetes originate, in part, from the progressive metabolic deterioration of skeletal muscle. A preliminary proteomic survey of rectus abdominus muscle detected a statistically significant increase in adenylate kinase (AK)1, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and aldolase A in obese/overweight and morbidly obese women relative to lean control subjects. AK1 is essential for the maintenance of cellular energy charge, and GAPDH and aldolase A are well known glycolytic enzymes. We found that muscle AK1 protein and enzymatic activity increased 2.9 and 90%, respectively, in obese women and 9.25 and 100%, respectively, in morbidly obese women. The total enzymatic activity of creatine kinase, which also regulates energy metabolism in muscle, was shown to increase 30% in obese/overweight women only. We propose that increased protein and enzymatic activity of AK1 is representative of a compensatory glycolytic drift to counteract reduced muscle mitochondrial function with the progression of obesity. This hypothesis is supported by increased abundance of the glycolytic enzymes GAPDH and aldolase A in obese and morbidly obese muscle. In summary, proteome analysis of muscle has helped us better describe the molecular etiology of obesity-related disease.

Footnotes

    • Accepted February 4, 2005.
    • Received November 24, 2004.
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