Abstract

The metabolism and composition of skeletal muscle tissue is of special interest because it is a primary site of insulin action and plays a key role in the pathogenesis of insulin resistance. Intramyocellular (IMCL) triglyceride stores are an accessible form of energy that may decrease skeletal muscle glucose utilization, thereby contributing to impaired glucose metabolism. Because of the invasive nature of muscle biopsies, there is limited, if any, information about intramuscular lipid stores in children. The development of (1)H nuclear magnetic resonance (NMR) spectroscopy provides a unique noninvasive alternative method that differentiates intracellular fat from intercellular fat in muscle tissue. The present study was performed to determine whether IMCL and extramyocellular (EMCL) lipid contents are increased early in the development of juvenile obesity and to explore the relationships between IMCL and EMCL to in vivo insulin sensitivity, independently of total body fat and central adiposity in obese and nonobese adolescents. Eight nonobese (BMI 21 kg/m(2), age 11-16 years) and 14 obese (BMI 35 +/- 1.5 kg/m(2), age 11-15 years) adolescents underwent 1) (1)H-NMR spectroscopy to noninvasively quantify IMCL and EMCL triglyceride content of the soleus muscle, 2) a 2-h euglycemic-hyperinsulinemic clamp (40 mU.m(-2).min(-1)) to assess insulin sensitivity, 3) a dual-energy X-ray absorptiometry scan to measure total percent body fat, and 4) magnetic resonance imaging to measure abdominal fat distribution. Both the IMCL and EMCL content of the soleus muscle were significantly greater in the obese adolescents than in the lean control subjects. A strong inverse correlation was found between IMCL and insulin sensitivity, which persisted and became even stronger after controlling for percent total body fat and abdominal subcutaneous fat mass (partial correlation r = -0.73, P < 0.01) but not when adjusting for visceral fat (r = - 0.54, P < 0.08). In obese adolescents, increase in total body fat and central adiposity were accompanied by higher IMCL and EMCL lipid stores. The striking relationships between both IMCL and EMCL with insulin sensitivity in childhood suggest that these findings are not a consequence of aging but occur early in the natural course of obesity.