Nonalcoholic fatty liver disease (NAFLD), the hepatic component of insulin resistance syndrome, is pathophysiologically associated with lower hepatic insulin clearance, lower fat oxidation and increased carbohydrate oxidation in a post-absorptive state. Aerobic exercise is purported to be beneficial in NAFLD. To better understand the mechanisms through which short-term, moderate intensity aerobic exercise training could exert these benefits, 13 obese, sedentary adults (age: 58±3.4 years, BMI: 34.3±1.1 kg/m2; means±SEM) with NAFLD (>5% Intra-hepatic lipid content assessed by 1H MR spectroscopy) were recruited into a 7-day exercise training program (treadmill walking for 60 mins, 5 days per week, at 80-85% maximum heart rate). Participants maintained their normal dietary patterns. Pre- and post-intervention assessments included a 75-gm OGTT, CT scans, VO2max and indirect calorimetry. Insulin sensitivity (ISI) was estimated using Soonthorpun model. Hepatic Insulin Extraction (HIE) was calculated as the molar difference in AUCs for insulin and C-peptide (HIE=1-(AUCInsulin÷AUCC-Pep)). The intervention yielded an ∼9% increase in VO2max and HIE (P<0.01). Whole-body insulin sensitivity increased by ∼43% (P<0.05). There was a significant increase in basal fat oxidation (pre vs. post: 47±6 vs. 65±6 mg/min, P<0.05) and decrease in basal carbohydrate oxidation (160±20 vs. 112±15 mg/min, P<0.05). After the intervention, HIE was positively correlated with adiponectin (r=0.56, P<0.05) and negatively correlated with TNF-α (r=-0.78, P<0.001). The change in ISI was negatively correlated with change in subcutaneous abdominal fat depot (r=-0.55, P=0.05). These data suggest that exercise may quickly reverse the pathophysiology of NAFLD by improving

HIE and fasting substrate oxidation. The cardio-metabolic benefit of exercise in individuals with NAFLD is potentially mediated through changes in HIE.


A. Hari: None. C.E. Fealy: None. J.P. Kirwan: None.

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