Ascorbic acid attenuates obesity induced myogenic impairment in C2C12 cells.

AIM: Obesity is commonly associated with skeletal muscle atrophy and is attributed to chronic inflammation, oxidative stress, and impaired adipose-muscle cross talk. Ascorbic acid, a potent antioxidant and its role in obesity induced muscle atrophy is not clearly understood. Hence, the aim of the study was to rescue obesity induced skeletal muscle atrophy with ascorbic acid in vitro.

MATERIALS AND

METHODS

C3H10T1/2 mesenchymal stem cells were developed into obesogenic adipocytes by palmitic acid treatment to generate obesogenic adipocyte-conditioned media (ObCM). C2C12 myoblasts and differentiated myotubes were treated with ObCM in the presence or absence of ascorbic acid (AsA). Cell viability and reactive oxygen species generation were evaluated by MTT assay and DCFDA staining. Gene and protein expression analyses were performed using quantitative real-time PCR and western blotting. Statistical significance was determined using one-way ANOVA with Tukey's post hoc test.

KEY FINDINGS: In the present study, we have established a palmitic acid induced hypertrophic adipocyte model using C3H10T1/2 mesenchymal stem cells and generated obese conditioned medium to replicate obese microenvironment. Differentiated C2C12 myotubes when exposed to obese conditioned media resulted in reduced myotube diameter, increased expression in ROS, inflammatory cytokines, activation of ubiquitin proteasome system and upregulated muscle atrophy genes. Treatment with Ascorbic acid significantly mitigated ROS generation, reduced inflammatory cytokines, and restored myogenic protein expression associated with modulation of NF-κB signalling.

SIGNIFICANCE: Our findings suggest that ascorbic acid alleviates adipocyte-derived inflammatory stress and protects against myotube atrophy, highlighting its therapeutic potential in obesity-associated muscle wasting.