Serum Follistatin Levels are Independently Associated with Exercise Tolerance in Patients with Obesity.

Objective: Follistatin (FST)/myostatin (MST) myokine-signaling axis is important for muscle metabolism and pathogenesis of obesity. FST, mainly secreted by skeletal muscle and liver, inhibits MST and affects skeletal muscle synthesis. This study aimed to identify the characteristics of myokines and independent predictors of serum FST levels in patients with obesity.

Methods: In this retrospective cross-sectional study, 226 patients (mean age, 46.6 years; men, 35.4%) with obesity who initially visited an outpatient clinic between June 2014 and September 2020, were included and classified into obesity (25.0 ≤ body mass index (BMI) < 35.0 kg/m²) and severe obesity (BMI ≥35 kg/m²) groups based on the guidelines of the Japan Society for the Study of Obesity. Body composition was measured using bioelectrical impedance analysis and computed tomography. Muscle strength, exercise tolerance, metabolic parameters, and myokines were measured, including serum levels of FST, MST, irisin, and brain-derived neurotrophic factor.

Results: Serum FST levels were significantly higher in the severe obesity group than in the obesity group (median: 768.4 vs. 895.1 pg/mL, P = 0.020). However, the levels of other myokines showed no significant differences between the groups. In Model 1, which included factors that significantly correlated with FST levels, stepwise multivariate regression analysis revealed peak oxygen uptake (VO₂) as an independent predictor of FST levels based on the significance of the univariate analysis. Additionally, Model 2 was analyzed by adding myokine level to Model 1, revealing that peak VO_2, MST, and irisin levels were independent predictors of FST levels.

Conclusion: Serum FST levels were higher in patients in the severe obesity group compared to those in the obesity group. There was an independent association between low exercise tolerance and elevated serum FST levels.