| Abstract | Non-Alcoholic Fatty Liver Disease (NAFLD) is associated with multi-organ (hepatic, skeletal muscle, adipose tissue) insulin resistance (IR). Exercise is an effective treatment for lowering liver fat but its effect on insulin resistance in NAFLD is unknown. We aimed to determine whether supervised exercise in NAFLD would reduce liver fat and improve hepatic and peripheral (skeletal muscle and adipose tissue) insulin sensitivity.Sixty nine NAFLD patients were randomised to 16 weeks exercise supervision ( n =38) orcounselling ( n =31) without dietary modification.All participants underwent magnetic resonance imaging/spectroscopy to assess changes in body fat, and in liver and skeletal muscle triglyceride, before and following exercise/counselling. To quantify changes in hepatic and peripheral insulin sensitivity, a pre-determined subset ( n =12 per group) underwent a two-stage hyperinsulinaemic euglycaemic clamp pre- and post-intervention. Results are shown as mean (95% CI). Fifty participants (30 exercise, 20 counselling), 51 y (40, 56), BMI 31 kg/m2 (29, 35) with baseline liver fat/water % of 18.8 % (10.7, 34.6) completed the study (12/12 exercise and 7/12 counselling completed the clamp studies). Supervised exercise mediated a greater reduction in liver fat/water % than counselling [Δ mean change 4.7% (0.01, 9.4); P <0.05], which correlated with the change in cardiorespiratory fitness (r = -0.34, P = 0.0173). With exercise, peripheral insulin sensitivity significant increased (following high-dose insulin) despite no significant change in hepatic glucose production (following low-dose insulin); no changes were observed in the control group. Although supervisedexercise effectively reduced liver fat, improving peripheralIR in NAFLD, the reduction in liver fat was insufficient to improve hepatic IR. |
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