THE ROLE OF INTRAMYOCELLULAR FATTY ACIDS ON THE ETIOLOGY OF THE INSULIN RESISTANCE OF OBESITY
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The intracellular concentration of fatty acids in insulin-sensitive cells is purported to be a key factor in the development of insulin resistance. It is hypothesized that the intramyocellular lipid (IMCL) concentration is correlated with the degree of insulin resistance (IR), and that a reduction in IMCL will have a more significant effect on IR than a reduction in body adipose tissue stores. This study assessed the effects of weight loss through dietary intervention on the IMCL and IR on a group of obese adults and explored the correlations between IR, IMCL, body mass index (BMI), serum triglycerides (TG), free fatty acids, and total body fat of obese adults with an otherwise similar group of lean individuals. Baseline tests were performed in lean and obese, including a 2 hour Oral Glucose Tolerance Test (OGTT), body composition measurement by Dual Energy X-Ray Absorptiometry (DEXA), and IMCL determination in the tibialis anterioris (TA) and soleus (SOL) muscles by proton magnetic resonance spectroscopy. The obese underwent insulin sensitivity assessment by the euglycemic-hyperinsulinemic clamp. Furthermore, they were instructed to follow a hypocaloric diet, and were subsequently re-evaluated after a weight loss of 8-10% of total body weight. Our results indicate that the obese group had significantly higher IMCL levels in the SOL muscle than the lean group. In both groups, there was a significant positive correlation of IR, assessed by Homeostasis Model Assessment Index (HOMA), with IMCL in the SOL muscle but not in the TA. IMCL in the SOL was an important predictor of IR by HOMA, after controlling for age, BMI, and TG. Weight loss resulted in a significant decrease in IR and IMCL in the TA, but not in the SOL muscle. There was no correlation between changes iii in IMCL in TA myocytes and in IR. Our data documented that reduction in IMCL stores might play an important role in insulin signaling.