Does irisin mediate metabolic effects of androgen deficiency? A cross-sectional study in men with chronic spinal cord injury

Study design: Retrospective study.

Objectives: To check the hypothesis that irisin could mediate systemic metabolic effects of testosterone in men with chronic spinal cord injury (SCI).

Setting: Spinal Unit of the San Raffaele Institute in Sulmona.

Methods: Fifteen men with chronic SCI admitted to a rehabilitation program were involved. They underwent clinical and biochemical evaluations. Irisin levels were measured with a high-sensitivity ELISA kit. Free testosterone levels were calculated (cFT) from total testosterone, sex hormone binding globulin, and albumin concentrations using the Vermeulen formula.

Results: Androgen deficiency (total testosterone <3 ng/ml and cFT <64 pg/ml) was found in 53% of participants and was associated with significantly lower irisin levels, higher body mass index (BMI), and higher triglycerides. Participants were engaged in significantly poorer leisure time physical activity (LTPA). Circulating irisin correlated with cFT (r = 0.55; p = 0.03) and both were negatively correlated with triglycerides levels, homeostatic model assessment of insulin resistance (HOMA-IR) and systemic inflammation, as assessed by erythrocyte sedimentation rate (ESR). Correlations with irisin did not reach statistical significance for either BMI (r = -0.40; p = 0.13) or LTPA (r = 0.46; p = 0.08). In bivariate linear regression models, lower irisin levels were significantly associated with higher triglycerides (β = -0.46; 95% CI: -0.75 to -0.16), HOMA-IR (β = -0.32; 95% CI: -0.63 to -0.004) and ESR (β = -0.89; 95% CI: -1.69 to -0.10) independently of cFT. Conversely, the negative associations of cFT with the same variables were lost after adjustment for irisin levels.

Conclusions: Spinal cord-injured men with androgen deficiency exhibit lower levels of irisin, which could mediate the systemic effects of testosterone.