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Diabetes 54:1283-1288, 2005
© 2005 by the American Diabetes Association, Inc.

Proteome Analysis of Skeletal Muscle From Obese and Morbidly Obese Women

Dustin S. Hittel1, Yetrib Hathout1, Eric P. Hoffman1, and Joseph A. Houmard2

1 Research Center for Genetic Medicine, Children’s National Medical Center, Washington, DC
2 Department of Exercise and Sport Science and the Human Performance Laboratory and Diabetes/Obesity Center, East Carolina University, Greenville, North Carolina

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.


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

Abbreviations: AK, adenylate kinase; AMPK, AMP-activated protein kinase; CK, creatine kinase; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HOMA, homeostasis model assessment; MALDI, matrix-assisted laser desorption/ionization; MS, mass spectrometry; pI, isoelectric point; TOF, time-of-flight


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Copyright © 2005 by the American Diabetes Association.