Proteome analysis of skeletal muscle from obese and morbidly obese women.
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.
Hittel
Dustin S
DS
Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA.
Hathout
Yetrib
Y
Hoffman
Eric P
EP
Houmard
Joseph A
JA
D000263:Adenylate Kinase / Q000378:metabolism; D015992:Body Mass Index; D003402:Creatine Kinase / Q000378:metabolism; D004072:Digitonin; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D009767:Obesity, Morbid / Q000378:metabolism*; D020543:Proteome; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D009124:Muscle Proteins; D020543:Proteome; D003402:Creatine Kinase; D000263:Adenylate Kinase; D004072:Digitonin