Ectopic lipid storage in non-alcoholic fatty liver disease is not mediated by impaired mitochondrial oxidative capacity in skeletal muscle

Background: Non-alcoholic fatty liver disease (NAFLD) is a condition characterised by a synergistic association between insulin resistance, obesity and ectopic fat. This disease state has an increased prevalence of type Π diabetes (T2DM) and cardiovascular disease (CVD), thought to be mediated by the insulin resistance. There is much evidence to support the hypothesis that mitochondrial function in skeletal muscle may be implicated in the development of insulin resistance and obesity. We aim to determine if mitochondrial dysfunction contributes to ectopic fat accumulation and the associated metabolic syndrome by altering the post-prandial energy storage. Methods: To test this hypothesis, we performed a cross sectional study of 17 patients with NAFLD and 18 controls. Baseline biochemistry, lipid profile, liver function tests (LFT’s) glucose and insulin levels were assessed. Measurement of insulin resistance was made using HOMA-IR. Assessment of body composition was measured using Tanita bio-impedance analysis (Tanita BC 420, Dolby Medical Stirling, UK). Magnetic Resonance Imaging (MRI) and 1H-Magnetic Resonance Spectroscopy (MRS) determined abdominal, visceral, subcutaneous, skeletal muscle and intra hepatic fat respectively. We measured mitochondrial function within the quadriceps muscle during the study by measuring Phosphocreatine (PCr) recovery kinetics using 31P MRS. This analysis was carried out in the NAFLD group and compared to healthy controls Results: Patients with NAFLD matched with control subjects for age, BMI and VO2max had evidence of ectopic fat (higher LF and VAT). Despite this no difference in mitochondrial function was apparent. Conclusions: Altered skeletal muscle mitochondrial function does not explain ectopic fat deposition in patients with NAFLD