Accelerated intramyocellular triglyceride synthesis in skeletal muscle of high-fat-induced obese rats.

Abstract

To test the hypothesis that the synthesis of intramyocellular triglycerides (imcTG) in skeletal muscle is increased in obese rats in which the content of imcTG is known to be abnormally high. Sprague-Dawley male lean and high-fat-induced obese rats were studied at the age of 4, 8 and 12 months after an overnight fast, awake. [U-(14)C]glycerol was continuously infused intravenously for 2 h followed by muscle biopsies, and intracellular glycerol incorporation into imcTG was determined. imcTG content, intramyocellular free glycerol concentration and specific activity, systemic glycerol flux and plasma glycerol, free fatty acid (FFA) and glucose concentrations were also determined. The rates of incorporation of intramyocellular glycerol into imcTG (nmol/g wet muscle/h) were markedly accelerated in obese rats compared to their lean littermates at all ages: 66+/-12 vs 12+/-2 (P=0.02) for gastrocnemius and 74+/-29 vs 31+/-7 (P=0.09) for soleus when 4 months old; 223+/-29 vs 58+/-27 (P=0.001) for gastrocnemius, 224+/-28 vs 70+/-21 (P=0.001) for soleus and 294+/-78 vs 49+/-22 (P=0.02) for tibialis anterior when 8 months old; and 25+/-4 vs 11+/-2 (P=0.01) for gastrocnemius and 22+/-8 vs 8.4+/-3 (P=0.04) for soleus when 12 months old. As expected, this was accompanied by a higher imcTG content in virtually all muscles at all ages tested. The synthesis of imcTG in skeletal muscle is grossly increased in obese rats, which likely contributes to abnormal imcTG accumulation.