Influence of High-Fat Diet and Sex on Connective Tissue in Carpal Tunnel Syndrome

ABSTRACT 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. 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 (24 male, 24 female) adult rabbits were split into four groups including HFD or standard diet with and without CTS induction. SSCT was collected for histological and gene expression analysis. HFD promoted SSCT thickening and upregulated profibrotic genes, including TGF-β. Fibrotic genes were differentially expressed in males and females. Interestingly while the overall prevalence of CTS is greater in women than in men, under conditions of metabolic dysfunction men have a higher incidence. This suggests a focus on metabolic and sex specific therapeutic strategies for the treatment of patients with CTS.