Exercise-induced alterations in intramyocellular lipids and insulin resistance: the athlete's paradox revisited

Abstract

We previously reported an "athlete's paradox" in which endurance-trained athletes, who possess a high oxidative capacity and enhanced insulin sensitivity, also have higher intramyocellular lipid (IMCL) content. The purpose of this study was to determine whether moderate exercise training would increase IMCL, oxidative capacity of muscle, and insulin sensitivity in previously sedentary overweight to obese, insulin-resistant, older subjects. Twenty-five older (66.4 +/- 0.8 yr) obese (BMI = 30.3 +/- 0.7 kg/m2) men (n = 9) and women (n = 16) completed a 16-wk moderate but progressive exercise training program. Body weight and fat mass modestly but significantly (P < 0.01) decreased. Insulin sensitivity, measured using the euglycemic hyperinsulinemic clamp, was increased (21%, P = 0.02), with modest improvements (7%, P = 0.04) in aerobic fitness (Vo2peak). Histochemical analyses of IMCL (Oil Red O staining), oxidative capacity [succinate dehydrogenase activity (SDH)], glycogen content, capillary density, and fiber type were performed on skeletal muscle biopsies. Exercise training increased IMCL by 21%. In contrast, diacylglycerol and ceramide, measured by mass spectroscopy, were decreased (n = 13; -29% and -24%, respectively, P < 0.05) with exercise training. SDH (19%), glycogen content (15%), capillary density (7%), and the percentage of type I slow oxidative fibers (from 50.8 to 55.7%), all P < or = 0.05, were increased after exercise. In summary, these results extend the athlete's paradox by demonstrating that chronic exercise in overweight to obese older adults improves insulin sensitivity in conjunction with favorable alterations in lipid partitioning and an enhanced oxidative capacity within muscle. Therefore, several key deleterious effects of aging and/or obesity on the metabolic profile of skeletal muscle can be reversed with only moderate increases in physical activity.

Figures

Fig. 1

Effect of exercise on insulin sensitivity. Insulin sensitivity was determined using a hyperinsulinemic euglycemic clamp prior to and subsequent to exercise training, as described in METHODS; n = 25. Glucose infusion rate (GIR) is expressed relative to fat-free mass (FFM). Statistical significance is indicated. Data are means ± SE. PRE, preintervention; POST, postintervention.

Fig. 2

Effects of exercise on substrate availability and capacity for oxidation. Histochemical analyses were performed on skeletal muscle biopsy samples obtained as described in METHODS; n = 25. A: intramyocellular lipid (IMCL) content was measured by Oil Red O staining. B: oxidative capacity was measured by succinate dehydrogenase (SDH) staining. C: glycogen content was measured by a Schiff’s reagent protocol. D: capillary density. E: percentage of type I slow oxidative fibers. Statistical significance is indicated. Data are means ± SE. AU, arbitrary units.

Fig. 3

Effects of exercise on diacylglycerol (DAG) and ceramide content. DAG (A) and ceramide (B) content were assessed from skeletal muscle biopsy samples as described in METHODS; n = 13. Statistical significance is indicated. Data are means ± SE.