Physical Activity, Intramuscular Fat, and Insulin Resistance

Abstract

0007 PURPOSE: Intramyocellular lipid (IMCL) has been associated with insulin resistance of obesity, type 2 diabetes (T2DM) and aging. However, younger endurance-trained athletes are markedly insulin sensitive despite having IMCL similar to those with T2DM, suggesting that this association may be modulated by the oxidative capacity of muscle. We examined the hypothesis that exercise training would increase IMCL, the oxidative capacity of skeletal muscle and insulin sensitivity in older previously sedentary subjects. METHODS: 14 women and 7 men (67.3 ± 0.7 years) participated in an exercise training program designed to elicit improvements in cardiorespiratory fitness (VO2max). Before and after training, histochemical studies of vastus lateralis muscle biopsies were performed to quantify changes in IMCL, oxidative capacity of muscle, and muscle fiber type (N = 13). Changes in muscle lipid content were measured in 8 additional subjects using a novel non-invasive MRI method. Insulin resistance was determined by either the hyperinsulinemic glucose clamp method (n = 8) or the Homeostatic Model Assessment of insulin resistance (HOMA IR)(n = 13). RESULTS: IMCL, quantified by Oil Red O staining (n = 13), increased (p<0.05) from 22.9 ± 1.9 to 25.9 ± 2.6 Arbitrary Units (AU). The oxidative capacity of muscle, determined by SDH staining intensity, significantly increased (p<0.05) from 75.2 ± 5.2 to 83.9 ± 3.6 AU. The percentage of type I fibers determined by anti-myosin immunohistochemistry significantly increased (p<0.05) from 35.4 ± 2.1 to 40.1 ± 2.3%. In this group, there was a trend for HOMA IR to improve as a marker of insulin resistance (2.69 ± 0.43 to 2.38 ± 0.34, P = 0.14). In another group of subjects (n = 8), skeletal muscle lipid content of the gastrocnemius increased following training (7.10 ± 5.84 vs. 10.13 ± 6.54 g/dl; p<0.05). In this group, insulin sensitivity determined by the glucose clamp increased from 10.6 ± 2.2 to 11.6 ± 2.1 mg/kgFFM/min (P<0.05). CONCLUSIONS: Increased IMCL, in the context of enhanced capacity for fat oxidation, may actually represent a positive adaptation to chronic exercise. Future studies should examine the mechanisms by which improved oxidative capacity of muscle is linked with diminished insulin resistance.