The effect of long term exercise on intrahepatic lipid and the insulin sensitivity of glucose and fatty acid metabolism in sedentary male subjects

Background and aims: Adaptive changes in fatty acid metabolism, liver and muscle fat content and adipocyte-derived cytokines may potentially explain the beneficial effects of exercise on insulin action. We investigated this in sedentary men before and after 6 weeks of supervised exercise. Materials and methods: Thirteen sedentary overweight male subjects (age 50 ± 304yr, BMI 28.2 ± 0.5) were recruited, seven were randomised to a 6 week exercise programme and six remained sedentary. After completion of the baseline (0 weeks) metabolic study and body composition measurements subjects who were allocated to the exercise group started the exercise programme. Subjects exercised at 60-85% ofV02 max for a minimum of 20 minutes at least 3 times a week for 6 weeks. Insulin sensitivity of fatty acid (NEFA) production rate (Ra), glycerol Ra, glucose Ra and glucose disposal rate (Rd) were measured with stable isotopes of palmitic acid, glycerol and glucose at 0 and 6 weeks with a 2 step hyperinsulinaemic euglycaemic clamp (step 1, 0.3 (low dose); step 2, 1.5 (high dose) mU. kg-I. min-I). Intrahepatocellular lipid (IHCL) and intramyocellular lipid (IMCL) were measured by magnetic resonance spectroscopy and visceral fat by cross-sectional CT scanning. Results: In the exercise group V02 max increased by 20 ± 5% after 6 weeks (p<O.Ol) but there was no significant change in the control group. There was no significant change in body weight or BMI in either group. After 6 weeks, the decrease in glucose Ra following low dose insulin was greater than at 0 week in the exercise group (3.8 ± 0.5 vs 2.8 ± O.5llmol.kg-l.min-t, 0 week vs 6 weeks, p<0.05) with no change in the control group (3.2 ± 0.7 vs 3.2±004llmol.kg-l.min-I). After 6 weeks the increase in the area under the curve for glucose Rd following high dose insulin was greater than at 0 week in the exercise group (5404 ± 7351lmol!kg vs 6508 ± 581llmol!kg, p<O.Ol) with no change in the control group (4664 ± 5381lffiol!kg vs 4628 ± 415 Ilmol!kg). In the exercise group there was a decrease in fasting NEFA concentration (0.81 ±0.04 vs 0.62 ± 0.05 mmol!l, 0 week vs 6 weeks, respectively, p<O.Ol), fasting glycerol concentration (75 ± 8.3 vs 58 ± 6.6Ilffiol!l, p<0.03), fasting glycerol Ra (3.3±0.8 vs 2.5±0.6Ilmol· kg-I. min-l ,p<0.02) and fasting NEFA Ra (4.5 ± 0.3 vs 3.7 ± 0.51lmol . kg-I . min-I, p<0.04), visceral fat content (186 ± 13 cm2 vs 152 ± 10 cm2, p<0.04) and fasting adiponectin (7.0 ± 0.91lglml vs 5.8 ± 0.9Ilg/ml, p<0.05) but no change in the control group. There was no change in IMCL in either group. The improved insulin sensitivity of glucose Ra in the exercise group correlated with a decrease in IHCL (p