title: Ectopic lipid storage in non-alcoholic fatty liver disease is not mediated by impaired mitochondrial oxidative capacity in skeletal muscle.
abstract: 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 that impaired skeletal muscle mitochondrial function may contribute to ectopic lipid deposition, and the associated MS, by altering post-prandial energy storage. To test this hypothesis, we performed a cross-sectional study of 17 patients with NAFLD [mean±S.D.; age, 45±11 years; body mass index (BMI), 31.6±3.4 kg/m2] and 18 age- and BMI-matched healthy controls (age, 44±11 years; BMI, 30.5±5.2 kg/m2). We determined body composition by MRI, IHCL and intramyocellular (soleus and tibialis anterior) lipids (IMCLs) by proton magnetic resonance spectroscopy (1H-MRS) and skeletal muscle mitochondrial function by dynamic phosphorus magnetic resonance spectroscopy (31P-MRS) of quadriceps muscle. Although matched for BMI and total adiposity, after statistical adjustment for gender, patients with NAFLD (defined by IHCL ≥ 5.5%) had higher IHCLs (25±16% compared with 2±2%; P<0.0005) and a higher prevalence of the MS (76% compared with 28%) compared with healthy controls. Despite this, the visceral fat/subcutaneous fat ratio, IMCLs and muscle mitochondrial function were similar between the NAFLD and control groups, with no significant difference in the rate constants of post-exercise phosphocreatine (PCr) recovery (1.55±0.4 compared with 1.51±0.4 min-1), a measure of muscle mitochondrial function. In conclusion, impaired muscle mitochondrial function does not seem to underlie ectopic lipid deposition, or the accompanying features of the MS, in patients with NAFLD.
authors.affiliation: *Department of Obesity and Endocrinology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, U.K.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Cuthbertson
authors.affiliation: *Department of Obesity and Endocrinology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, U.K.
authors.forename: Andrew
authors.initials: A
authors.lastname: Irwin
authors.forename: Victoria S
authors.initials: VS
authors.lastname: Sprung
authors.affiliation: †Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, U.K.
authors.forename: Helen
authors.initials: H
authors.lastname: Jones
authors.affiliation: †Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, U.K.
authors.forename: Christopher J A
authors.initials: CJ
authors.lastname: Pugh
authors.affiliation: *Department of Obesity and Endocrinology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, U.K.
authors.forename: Christina
authors.initials: C
authors.lastname: Daousi
authors.affiliation: ‡Magnetic Resonance and Image Analysis Research Centre (MARIARC), University of Liverpool, Liverpool, U.K.
authors.forename: Valerie L
authors.initials: VL
authors.lastname: Adams
authors.affiliation: ‡Magnetic Resonance and Image Analysis Research Centre (MARIARC), University of Liverpool, Liverpool, U.K.
authors.forename: William E
authors.initials: WE
authors.lastname: Bimson
authors.affiliation: §Diabetes and Metabolic Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, U.K.
authors.forename: Fariba
authors.initials: F
authors.lastname: Shojaee-Moradie
authors.affiliation: ∥Department of Hepatology, Royal Liverpool University Hospital, Liverpool, U.K.
authors.forename: Paul
authors.initials: P
authors.lastname: Richardson
authors.affiliation: §Diabetes and Metabolic Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, U.K.
authors.forename: A Margot
authors.initials: AM
authors.lastname: Umpleby
authors.affiliation: *Department of Obesity and Endocrinology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, U.K.
authors.forename: John P
authors.initials: JP
authors.lastname: Wilding
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Kemp
mesh_terms: D000328:Adult; D001823:Body Composition; D003430:Cross-Sectional Studies; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000473:pathology; D050356:Lipid Metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease; D050151:Subcutaneous Fat / Q000473:pathology