Combined feed restriction and exercise uniquely modulate exercise-induced inflammatory responses in overweight horses

Background Equine obesity is linked to low-grade inflammation. Feed restriction may impair gastrointestinal function. Exercise may offer an alternative, though adiposity-exercise interactions remain unclear. Objective To evaluate exercise-induced changes in inflammatory-related signaling and cartilage metabolism in blood and synovial fluid following feed restriction, exercise, or both. Methods Overweight horses were assigned to feed restriction (FR; n=6; 85% DE), exercise (E; n=7; 30 min/day, 5 days/week; 100% DE), combined feed restriction and exercise (FRE; n=8; 85% DE + exercise), or control (C; n=7; 100% DE, no exercise) for 10 weeks. Blood and synovial fluid were collected pre-SET and 1, 8, and 12 h post-SET in Weeks 1 and 10 and analyzed for prostaglandin E 2 (PGE 2 ), nitric oxide (NO), resolvin D1 (RvD1), and glycosaminoglycan (GAG). Results At Week 10, synovial fluid log(PGE 2 ) decreased (1.15 ± 0.16 vs. 1.66 ± 0.18 pg/mL; p=0.04), while synovial fluid NO (6.31 ± 0.58 vs. 3.56 ± 0.63 μg/mL; p=0.002), plasma NO (5.29 ± 0.15 vs. 4.90 ± 0.15 μg/mL; p=0.04), and plasma GAG (2.73 ± 0.24 vs. 1.97 ± 0.25 μg/mL; p=0.04) increased. In Week 10, synovial fluid NO at 12 h post-SET was greater in FRE (20.9 ± 3.18 μg/mL) than C (4.96 ± 2.24; p<0.001), FR (5.17 ± 2.59; p<0.001), and E (10.0 ± 2.59; p=0.02). FRE also had higher synovial fluid GAG (8.41 ± 0.81 μg/mL) than C (5.14 ± 0.68; p=0.01) and FR (4.48 ± 0.76; p=0.003). Conclusion Combined feed restriction and exercise modulate inflammatory signaling and cartilage turnover following exercise.