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 IR 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 randomized to 16 weeks exercise supervision (n=38) or counselling (n=31) without dietary modification. All participants underwent MRI/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% confidence interval (CI)]. Fifty participants (30 exercise, 20 counselling), 51 years (IQR 40, 56), body mass index (BMI) 31 kg/m(2) (IQR 29, 35) with baseline liver fat/water % of 18.8% (IQR 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 percentage 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 significantly increased (following high-dose insulin) despite no significant change in hepatic glucose production (HGP; following low-dose insulin); no changes were observed in the control group. Although supervised exercise effectively reduced liver fat, improving peripheral IR in NAFLD, the reduction in liver fat was insufficient to improve hepatic IR.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of histopathological abnormalities which increase the risk of chronic liver disease, hepatocellular carcinoma and cardiovascular disease [1].Non-Alcoholic Fatty Liver Disease (NAFLD) arises from accumulation of liver fat, frequently complicating obesity and other insulinresistant states, co-existing with the metabolic syndrome [2, 3]
An equal number (n=15) completed the exercise in each centre; 8 controls completed in Liverpool and 12 controls completed in Guildford, Surrey
We have demonstrated in a randomised controlled study that 16 weeks of supervised moderateintensity aerobic exercise in NAFLD reduces liver fat and that this was correlated with an improvement in cardiorespiratory fitness
Summary
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of histopathological abnormalities which increase the risk of chronic liver disease, hepatocellular carcinoma and cardiovascular disease [1].NAFLD arises from accumulation of liver fat, frequently complicating obesity and other insulinresistant states, co-existing with the metabolic syndrome [2, 3]. Various modalities of exercise have been shown to be beneficial in reducing liver fat in NAFLD including aerobic [5, 14, 15] and resistance exercise [13], even without weight loss. A recent study addressing the dose-response relationship between aerobic exercise and reduction in liver fat suggests that even low volume, low intensity aerobic exercise can reduce liver fat without clinically significant weight loss [16]. It is unclear to what extent reduction in liver fat following exercise is associated with improvements in hepatic and peripheral IR. This is of particular importance considering the high rates of incident type diabetes mellitus (T2DM) in NAFLD patients
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