Background

Growth differentiation factor 15 (GDF15) is an anti-obesity agent that may benefit non-alcoholic fatty liver disease (NAFLD), as it improves insulin sensitivity and reduces liver fat in pre-clinical models.However, whether metabolic improvements occur without weight loss is unknown.In humans, exercise increases GDF15. Thus, we evaluated the effects of a 7-day, weight stable, exercise intervention on circulating GDF15 concentrations and associated metabolic improvements in adults with NAFLD.

Methods

Twenty-eight adults (age: 54±2, BMI: 32.9± 0.8, kg/m2) underwent H1-MRS scans for assessment of hepatic triglyceride content (HTGC) and composition, and 20 adults met the NAFLD diagnostic criteria (HTGC>5.5%). A subgroup (CNTL: n=5, NAFLD: n=14) participated in 7 days of aerobic exercise training (60 min/day at ~85% HRmax). Pre/post measurements included body composition (DXA), plasma GDF15 (ELISA), and insulin resistance measures (OGTT).

Results

At baseline, GDF15 was elevated in the NAFLD group versus controls (NAFLD: 873.9±87.3, CNTL: 558.5±65.9, pg/ml, P=0.04). Within the NAFLD group, GDF15 negatively correlated with hepatic saturated fat (r= -0.50, P=0.03). Exercise training further increased plasma GDF15 (Pre: 861.9± 97.4, Post: 950.6±114.5, pg/ml, P=0.02) in the NAFLD group, and was accompanied by increased hepatic polyunsaturated lipids (Pre: 0.6±0.1, Post, 0.7±0.1%, P=0.05), increased insulin sensitivity, (Pre: 1.3±0.1, Post: 1.7±0.2, Matsuda index, P=0.002), and reduced insulin resistance (Pre: 8.3±1.0, Post: 6.2±0.7, HOMA-IR, P=0.01). Changes in GDF15 correlated with improved insulin sensitivity (r=0.59, P=0.03) and reduced insulin resistance (r=-0.64, P=0.01). Weight and body composition remained stable during the intervention.

Conclusions

We report links between short term exercise-induced GDF15 and improved hepatic lipid storage and glucose metabolism in adults with NAFLD, suggesting a beneficial role of GDF15 in NAFLD management independent of weight loss.