title: 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.
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.
authors.affiliation: 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. daniel.cuthbertson@liv.ac.uk.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Cuthbertson
authors.affiliation: Diabetes and Metabolic Medicine, Faculty of Health and Medical Sciences, University of Surrey, GU2 7WG, U.K.
authors.forename: Fariba
authors.initials: F
authors.lastname: Shojaee-Moradie
authors.affiliation: 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.
authors.forename: Victoria S
authors.initials: VS
authors.lastname: Sprung
authors.affiliation: Research Institute for Sport and Exercise Science, Liverpool John Moores University, Liverpool, L3 5UA, U.K.
authors.forename: Helen
authors.initials: H
authors.lastname: Jones
authors.affiliation: Research Institute for Sport and Exercise Science, Liverpool John Moores University, Liverpool, L3 5UA, U.K.
authors.forename: Christopher J A
authors.initials: CJ
authors.lastname: Pugh
authors.affiliation: Department of Hepatology, Royal Liverpool University Hospital, L7 8XP, U.K.
authors.forename: Paul
authors.initials: P
authors.lastname: Richardson
authors.affiliation: 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.
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Kemp
authors.affiliation: Diabetes and Metabolic Medicine, Faculty of Health and Medical Sciences, University of Surrey, GU2 7WG, U.K.
authors.forename: Mark
authors.initials: M
authors.lastname: Barrett
authors.affiliation: Diabetes and Metabolic Medicine, Faculty of Health and Medical Sciences, University of Surrey, GU2 7WG, U.K.
authors.forename: Nicola C
authors.initials: NC
authors.lastname: Jackson
authors.affiliation: Metabolic and Molecular Imaging Group, MRC Clinical Sciences Centre, Imperial College London, London, SW7 2AZ, U.K.
authors.forename: E Louise
authors.initials: EL
authors.lastname: Thomas
authors.affiliation: Metabolic and Molecular Imaging Group, MRC Clinical Sciences Centre, Imperial College London, London, SW7 2AZ, U.K.
authors.forename: Jimmy D
authors.initials: JD
authors.lastname: Bell
authors.affiliation: Diabetes and Metabolic Medicine, Faculty of Health and Medical Sciences, University of Surrey, GU2 7WG, U.K.
authors.forename: A Margot
authors.initials: AM
authors.lastname: Umpleby
mesh_terms: D015444:Exercise / Q000502:physiology*; D005223:Fats / Q000032:analysis / Q000378:metabolism; D005260:Female; D015309:Glucose Clamp Technique; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008099:Liver / Q000737:chemistry* / Q000503:physiopathology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000737:chemistry / Q000503:physiopathology; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D009765:Obesity / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D010809:Physical Fitness / Q000502:physiology; D014280:Triglycerides / Q000032:analysis
chemical_list: D005223:Fats; D014280:Triglycerides
keywords: exercise; insulin resistance; liver fat and magnetic resonance spectroscopy; non-alcoholic fatty liver disease (NAFLD)