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 (original) (raw)
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Representative photograph of Massons's trichrome-stained section of an epidermal wound in a mouse with streptozotocin-induced diabetes treated with a kinin B2 receptor antagonist. For further information please see pp. 45-56. Original image courtesy of D. Desposito, C. Chollet, C. Taveau, V. Descamps, F. Alhenc-Gelas, R. Roussel, N. Bouby and L. Waeckel.
Research Article| December 09 2015
*Department of Obesity and Endocrinology, University Hospital Aintree, L9 7AL, U.K.
†Institute of Ageing and Chronic Disease, University of Liverpool, L69 3GA, U.K.
‡Department of Musculoskeletal Biology and MRC–Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA), University of Liverpool, L69 3GA, U.K.
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§Diabetes and Metabolic Medicine, Faculty of Health and Medical Sciences, University of Surrey, GU2 7WG, U.K.
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*Department of Obesity and Endocrinology, University Hospital Aintree, L9 7AL, U.K.
†Institute of Ageing and Chronic Disease, University of Liverpool, L69 3GA, U.K.
‡Department of Musculoskeletal Biology and MRC–Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA), University of Liverpool, L69 3GA, U.K.
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║Research Institute for Sport and Exercise Science, Liverpool John Moores University, Liverpool, L3 5UA, U.K.
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║Research Institute for Sport and Exercise Science, Liverpool John Moores University, Liverpool, L3 5UA, U.K.
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¶Department of Hepatology, Royal Liverpool University Hospital, L7 8XP, U.K.
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†Institute of Ageing and Chronic Disease, University of Liverpool, L69 3GA, U.K.
‡Department of Musculoskeletal Biology and MRC–Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA), University of Liverpool, L69 3GA, U.K.
**Magnetic Resonance and Image Analysis Research Centre (MARIARC), University of Liverpool, L69 3GA, U.K.
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§Diabetes and Metabolic Medicine, Faculty of Health and Medical Sciences, University of Surrey, GU2 7WG, U.K.
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§Diabetes and Metabolic Medicine, Faculty of Health and Medical Sciences, University of Surrey, GU2 7WG, U.K.
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††Metabolic and Molecular Imaging Group, MRC Clinical Sciences Centre, Imperial College London, London, SW7 2AZ, U.K.
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††Metabolic and Molecular Imaging Group, MRC Clinical Sciences Centre, Imperial College London, London, SW7 2AZ, U.K.
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§Diabetes and Metabolic Medicine, Faculty of Health and Medical Sciences, University of Surrey, GU2 7WG, U.K.
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Publisher: Portland Press Ltd
Received: June 25 2015
Revision Received: September 01 2015
Accepted: September 30 2015
Accepted Manuscript online: September 30 2015
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 Authors; published by Portland Press Limited
2016
Clin Sci (Lond) (2016) 130 (2): 93–104.
Revision Received:
September 01 2015
Accepted:
September 30 2015
Accepted Manuscript online:
September 30 2015
Citation
Daniel J. Cuthbertson, Fariba Shojaee-Moradie, Victoria S. Sprung, Helen Jones, Christopher J.A. Pugh, Paul Richardson, Graham J. Kemp, Mark Barrett, Nicola C. Jackson, E. Louise Thomas, Jimmy D. Bell, A. Margot Umpleby; 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. _Clin Sci (Lond) 1 January 2016; 130 (2): 93–104. doi: https://doi.org/10.1042/CS20150447
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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.
© 2016 Authors; published by Portland Press Limited
2016
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