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

Abstract

Word Count (excluding abstract, figures, tables and references) 3437The authors have nothing to declare Cuthbertson et al. 2013 2 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. It has been suggested that impaired skeletal muscle mitochondrial function may contribute to ectopic lipid deposition, and the associated metabolic syndrome, by altering post-prandial energy storage. To test this hypothesis, we performed a cross-sectional study of 17 patients with NAFLD (mean ± SD; age 45±11 y; BMI 31.6±3.4 kg/m 2 ) and 18 age-and BMI-matched healthy controls (age 44±11 y; BMI 30.5±5.2 kg/m 2 ). We determined body composition by magnetic resonance imaging (MRI), IHCL and intramyocellular (soleus and tibialis anterior) lipids (IMCL) by proton magnetic resonance spectroscopy ( 1 H-MRS) and skeletal muscle mitochondrial function by dynamic phosphorus magnetic resonance spectroscopy ( 31 P-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 IHCL (25±16 vs. 2±2 %; p<0.0005), and a higher prevalence of the metabolic syndrome (76 vs. 28%) compared with healthy controls. Despite this, visceral: subcutaneous fat ratio, IMCL and muscle mitochondrial function were similar between the NAFLD and control groups, with no significant difference in the rate constants of postexercise PCr recovery (1.55±0.4 vs. 1.51±0.4 min -1 ), a measure of muscle mitochondrial function. Impaired muscle mitochondrial function does not appear to underlie ectopic lipid deposition, or the accompanying features of the metabolic syndrome, in patients with NAFLD.

Nutrition: a promising route for prevention and management of obesity-related nonalcoholic fatty liver disease

“…Recently, authors provided evidence that skeletal muscle mitochondrial function is preserved in patients with NAFLD, compared with age, BMI and fitness-matched healthy controls, and cannot account for ectopic fat deposition or the high prevalence of metabolic syndrome. This research confirms that factors other than skeletal muscle mitochondrial dysfunction play a role in NAFLD, suggesting that skeletal muscle and adipose tissue IR play a major role [6]. NAFLD is a multifactorial disease that involves a complex interaction of genetics, diet, and lifestyle, all of which combine to form the NAFLD phenotype.…”

“…NAFLD is a multifactorial disease that involves a complex interaction of genetics, diet, and lifestyle, all of which combine to form the NAFLD phenotype. NAFLDor generally speaking hepatic steatosis (HS) -is defined as the accumulation of lipid, primarily in the form of triacylglycerols in individuals who do not consume significant amounts of alcohol ( < 20 g ethanol/day) and in whom other known causes of steatosis, such as certain drugs and toxins, have been excluded [6]. The spectrum of NAFLD includes simple fatty liver (FL), also thought to be benign, nonalcoholic steatohepatitis (NASH) -characterized by inflammation, apoptosis, ballooning degeneration, Mallory hyaline, fibrosis -cirrhosis post NASH, hepatocellular carcinoma and advanced liver disease, which leads to liver-related death Although NAFLD is usually obesity-related, patients not clearly obese (BMI > 30) may show features of hepatic stetosis, called by some authors lean NAFLD or better non-obese-NAFLD.…”

Biomarkers in Nonalcoholic Fatty Liver Disease

“…In these studies, body mass index or waist circumference, AST, ALT, GGT, triglycerides, glucose, insulin and the homeostasis model assessment of insulin resistance were either significantly higher or showed a trend toward higher levels in NAFLD patients compared with healthy controls. Total cholesterol and low-density lipoprotein levels were similarly higher and high-density lipoprotein levels were lower, with trends observed in smaller samples (30,92,94,(96)(97)(98)(99)(100)(101)(102)(103)(104)(105)(106)(107)(108). Diabetes mellitus, MS and hypertension were significantly more predominant in NAFLD patients than in controls in these samples (30,92,(98)(99)(100)(101)103,107).…”

“…Several studies assessed biochemical parameters in NAFLD patients and healthy controls (30,92,94,(96)(97)(98)(99)(100)(101)(102)(103)(104)(105)(106)(107)(108). In these studies, body mass index or waist circumference, AST, ALT, GGT, triglycerides, glucose, insulin and the homeostasis model assessment of insulin resistance were either significantly higher or showed a trend toward higher levels in NAFLD patients compared with healthy controls.…”

Physical activity intervention for non-diabetic patients with non-alcoholic fatty liver disease: a meta-analysis of randomized controlled trials

“…Nineteen studies were excluded after the full text was reviewed. Finally, 9 studies involving 951 participants were included in the meta-analysis [8,[14][15][16][17][18][19][20][21]. Among them, 2 studies [17,21] had more than one intervention groups, therefore each type of intervention was compared with control group and analyzed.…”