Proteome analysis of skeletal muscle from obese and morbidly obese women.

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.

• Authors: Dustin S Hittel, Yetrib Hathout, Eric P Hoffman, Joseph A Houmard
• Journal: Diabetes (Diabetes) Vol. 54 Issue 5 Pg. 1283-8 (May 2005) ISSN: 0012-1797 [Print] United States
• PMID: 15855311 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Muscle Proteins
• Proteome
• Creatine Kinase
• Adenylate Kinase
• Digitonin

Topics

• Adenylate Kinase (metabolism)
• Body Mass Index
• Creatine Kinase (metabolism)
• Digitonin
• Electrophoresis, Gel, Two-Dimensional
• Female
• Humans
• Middle Aged
• Muscle Proteins (metabolism)
• Obesity (metabolism)
• Obesity, Morbid (metabolism)
• Proteome
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization