Background

Both obesity and idiopathic inflammatory myopathy (IIM) are associated with changes in muscle metabolism. Exercise improves muscle function and metabolism, providing benefits for patients’ clinical state. Effects of training on fat oxidative capacity (FOx) of differentiated muscle cells (myotubes) from patients with IIM was evaluated and compared to cells from healthy age/BMI-matched controls (n=7/7).

Methods

Patients underwent 6-month intense supervised activities of daily living & resistance training. DEXA (body composition) & muscle biopsy were performed (Bergstrom needle) before and after training. Muscle cells were cultured and exposed to 3-day 100μM palmitate during differentiation. Complete (CO2) & incomplete (ASP) FOx as well as an acute response to 100μM palmitate were assessed using [1-14C]-palmitate in cells with/without 3-day palmitate exposure. OXPHOS content was determined (WB).

Results

Three-day palmitate exposure increased complete (CO2 p<0.05) & incomplete (ASP p<0.01) FOx. During 3h 100μM palmitate challenge, myotubes from sedentary but not trained patients produced less ASP than healthy controls (p<0.05), independent on 3-day palmitate exposure (ASP p<0.1). Capacity to increase FOx (ASP) after 3-day palmitate tended to be reduced in myotubes from patients vs. controls (p<0.1), independent from patients’ training state. Accordingly, 3-day palmitate tended to increase mitochondrial complex V only in myotubes from healthy controls (p<0.1). Proportion of complete FOx correlated negatively with BMI (R=-0.51; p=0.02), fat mass (R=-0.59; p=0.006) & BF% (R=-0.516, p=0.017).

Conclusions

Myotubes from patients with myopathy had lower capacity for fat oxidation than those from healthy controls and intense 6-month exercise mitigated this disease effect. Moreover, capacity for complete fat oxidation was negatively associated with adiposity, suggesting that intrinsic defects of muscle fat oxidation contribute to the obese phenotype. Grants: MZCR 16-33746A, VEGA 2/0091/19, MZCR 16-33574A