Impact of obesity and an obesogenic environment on cardiotoxin‐induced damage and recovery of human myotubes

Obesity (BMI ≥ 30 kg/m²) reduces skeletal muscle quality and impairs the myogenic response to muscle damage. The present study investigated if differences exist in myotubes from individuals with (OB) or without (LN) obesity incubated in control (bovine serum albumin [BSA]) or obesogenic (Ob) medium, at baseline or in response to cardiotoxin (CTX)-induced damage and recovery. Differentiated, primary human myotubes from LN and OB donors were cultured in control (BSA-DM) or (Ob-DM) (250 µM palmitate, 250 µM oleate, 100 nM insulin, and 2.5 ng/mL tumour necrosis factor) differentiation medium (DM) for 48 h and treated with 1.0 µM CTX or vehicle control for 1 h (immediately post [IP]). Myotubes recovered in Ob (Ob-GM) or BSA (BSA-GM) growth medium (GM) for 3 days (3D). At baseline, myotubes (LN and OB) incubated in Ob-DM had 5% lower fusion index (FI) and nuclei/tube than BSA-DM. At IP post-CTX, there were no differences in FI or membrane integrity (lactate dehydrogenase), but the reduction in cell viability was greater in OB than LN myotubes and greater in myotubes (LN and OB) incubated in Ob-DM than BSA-DM. At 3D post-CTX, total nuclei, FI, and nuclei/tube were ∼15% lower in myotubes (LN and OB) incubated in Ob-GM than BSA-GM. Expressed as recovery (3D-IP) post-CTX, Ob-GM lowered total nuclei and FI in myotubes without differences between LN and OB. In human myotubes, impaired formation and recovery following damage in obesity appear primarily due to the obesogenic environment rather than inherent, individual differences.