Objective: Lifestyle intervention with diet modification and increase in physical activity is effective to reduce hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD). However, for a similar weight loss, there is a large variability in change in liver fat. We hypothesized that cardiorespiratory fitness may predict the response to the intervention.
Design: Longitudinal study with increase in physical activity and diet modification.
Setting: University teaching hospital.
Patients: 50 adults with NAFLD and 120 controls at risk for metabolic diseases.
Main outcome measures: Total-, subcutaneous abdominal- and visceral adipose tissue by magnetic resonance (MR) tomography, liver fat by 1HMR spectroscopy and cardiorespiratory fitness (VO2max) by a maximal cycle exercise test at baseline and after 9 months of follow-up.
Results: In all subjects total-, subcutaneous abdominal- and visceral adipose tissue decreased and fitness increased (all p<0.0001) during the intervention. The most pronounced changes were found for liver fat (-31 %, p<0.0001). Among the parameters predicting the change in liver fat, fitness at baseline emerged as the strongest factor, independently of total- and visceral adipose tissue as well as exercise intensity (p=0.005). In the group of subjects with NAFLD at baseline, a resolution of NAFLD was found in 20 individuals. For 1 standard deviation increase in VO2max at baseline the odds ratio for resolution of NAFLD was 2.79 (95% CI, 1.43 - 6.33).
Conclusions: Cardiorespiratory fitness, independently of total adiposity, body fat distribution and exercise intensity, determines liver fat content in humans, suggesting that fitness and liver fat are causally related to each other. Moreover, measurement of fitness at baseline predicts the effectiveness of a lifestyle intervention in reducing hepatic steatosis in patients with NAFLD.