Endurance Exercise Reduces Hepatic Fat Content and Serum Fibroblast Growth Factor 21 Levels in Elderly Men

Context: Age-related hepatic fat accumulation increases the risk of cardiometabolic diseases, and the fibroblast growth factor (FGF) 21-resistant state caused by fatty liver underlies the pathogenesis of these diseases. Objective: Previous studies suggested that a higher level of cardiorespiratory fitness was associated with both lower hepatic fat content and serum FGF21 levels; however, the effect of endurance exercise on hepatic fat content and serum FGF21 concentration has not been studied. Therefore, we aimed to elucidate whether endurance exercise reduced hepatic fat content and serum FGF21 levels. Design: This is a randomized crossover trial. Setting: The study setting was an institutional practice. Patients: Thirty-three elderly Japanese men participated in the study. Intervention: The intervention was a 5-week endurance exercise program comprising three cycle ergometer sessions per week. Main Outcome Measures: Hepatic fat content was assessed by proton magnetic resonance spectroscopy, and serum FGF21 level was determined by ELISA. Results: A5-week endurance exercise program decreased the hepatic fat content and serum FGF21 levels without weight loss, and the changes were higher in the exercise period than in the control period (P = .021 and P = .026, respectively). Correlation analysis demonstrated that only the change in hepatic fat content was significantly and positively correlated with change in serum FGF21 levels (r = 0.366, P = .006). Conclusions: A 5-week endurance exercise program decreased hepatic fat content and serum FGF21 levels without weight loss in elderly men, and exercise-induced hepatic fat reduction mediated the reduction in serum FGF21 levels. These findings suggest that endurance exercise modulates hepatic fat content and FGF21 resistance, regardless of obesity status.