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±11years; body mass index (BMI), 31.6±3.4kg/m2] and 18 age- and BMI-matched healthy controls (age, 44±11years; BMI, 30.5±5.2kg/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.
Highlights
Non-alcoholic fatty liver disease (NAFLD) describes a pathological spectrum in which lipid excessively accumulates within the liver, with or without associated necroinflammatory changes
The major finding of this study is that skeletal muscle mitochondrial function, determined using dynamic 31P-MRS measurements after exercise, is similar in patients with NAFLD to age, BMI- and cardiorespiratory fitness-matched controls
The similarity in mitochondrial function was observed despite greater liver fat deposition and more numerous components of the metabolic syndrome in patients with NAFLD suggesting that factors other than skeletal muscle mitochondrial dysfunction play a pathophysiological role in the metabolic phenotype of NAFLD
Summary
Non-alcoholic fatty liver disease (NAFLD) describes a pathological spectrum in which lipid excessively accumulates within the liver, with or without associated necroinflammatory changes. The association of NAFLD with insulin resistance, the metabolic syndrome and type 2 diabetes mellitus is well established [1]. It is well established that intracellular lipid accumulation within muscle and liver accompanies systemic insulin resistance, and mechanisms have been proposed for causal pathophysiological links between lipid accumulation and impaired insulin signaling [4, 5] the extent to which mitochondrial dysfunction contributes to accumulation of lipid in nonadipose sites, including skeletal muscle and liver, remains contentious. Some studies have suggested that defects in skeletal muscle mitochondrial oxidative capacity might contribute to ectopic lipid accumulation [2, 3, 6, 7] while others have found no significant association between ectopic fat deposition and altered mitochondrial function [8, 9]. The experimental literature in this area has been complicated by the variety of ways in which mitochondrial function can be assessed [10]
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