Influence of high-fat diet and sex on connective tissue in carpal tunnel syndrome

Carpal tunnel syndrome (CTS) is a common musculoskeletal disorder, characterized by thickening and fibrosis of the subsynovial connective tissue (SSCT). Risk factors for CTS includes sex, metabolic dysfunction and age. Interestingly although the overall prevalence of CTS is higher in women than in men, men exhibit a greater incidence under conditions of metabolic dysfunction. This suggests a focus on metabolic and sex specific therapeutic strategies for the treatment of patients with CTS. In this study we hypothesized that a high-fat diet (HFD), a common driver of metabolic dysfunction, would promote SSCT thickening in CTS and that this response would be sex dependent. To test this, we examined the effects of HFD and sex on SSCT thickening and markers of fibrosis using our established CTS rabbit model of SSCT thickening. Forty-eight mature adult rabbits (24 male and 24 female) were assigned to four groups including HFD or standard diet (STD), each with and without CTS induction. SSCT was collected for histological and gene expression analysis. Here we found that HFD promoted SSCT thickening and upregulated profibrotic genes, including TGF-β, with additional fibrotic genes exhibiting sex-specific differential expression.