Dissociation between exercise-induced reduction in liver fat and changes in hepatic and peripheral glucose homoeostasis in obese patients with non-alcoholic fatty liver disease
Pugh, Christopher J. A.
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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/m2 (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.
Cuthbertson, D.J., Shojaee-Moradie, F., Sprung, V.S., Jones, H., Pugh, C.J., Richardson, P., Kemp, G.J., Barrett, M., Jackson, N.C., Thomas, E.L., Bell, J.D. & Umpleby, M. (2016) 'Dissociation between exercise-induced reduction in liver fat and changes in hepatic and peripheral glucose homoeostasis in obese patients with non-alcoholic fatty liver disease', Clinical Science, 130(2), pp.93-104.
Dynodwr Gwrthrych Digidol (DOI)https://doi.org/10.1042/CS20150447
This article was published in Clinical Science available at https://doi.org/10.1042/CS20150447
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Exercise-induced improvements in liver fat and endothelial function are not sustained 12 months following cessation of exercise supervision in non-alcoholic fatty liver disease (NAFLD) Pugh, Christopher J. A.; Sprung, Victoria; Jones, Helen; Richardson, Paul; Shojaee-Morade, Faribra; Umpleby, A. Margot; Green, Daniel J.; Cable, N. Timothy; Trennel, Michael I.; Kemp, Graham J.; Cuthbertson, Daniel J. (Nature Publishing Group, 2016-07-21)AIMS: Supervised exercise reduces liver fat and improves endothelial function, a surrogate of cardiovascular disease risk, in non-alcoholic fatty liver disease (NAFLD). We hypothesised that after a 16-week supervised ...
Ectopic lipid storage in non-alcoholic fatty liver disease is not mediated by impaired mitochondrial oxidative capacity in skeletal muscle Cuthbertson, Daniel; Irwin, Andrew; Sprung, Victoria; Jones, Helen; Pugh, Christopher J. A.; Daousi, Christina; Adams, Valerie; Bimson, William; Shojaee-Moradie, Fariba; Richardson, Paul; Umpleby, Margot; Wilding, John; Kemp, Graham (Portland Press, 2014-12)Non-alcoholic fatty liver disease (NAFLD), characterized by lipid deposition within the liver [intrahepatocellular lipid (IHCL)], is associated with insulin resistance and the metabolic syndrome (MS). It has been suggested ...
Pugh, Christopher J. A.; Sprung, Victoria S.; Kemp, Graham J.; Richardson, Paul; Shojaee-Moradie, Fariba; Umpleby, A. Margot; Green, Daniel J.; Cable, N. Timothy; Jones, Helen; Cuthbertson, Daniel J. (American Physiological Society, 2014-11-01)Nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for cardiovascular disease (CVD). Endothelial dysfunction is an early manifestation of atherosclerosis and an important prognostic marker for future ...