RXRs expression in skeletal muscle in relationship with insulin sensitivity in normal-weight and obese volunteers.

Abstract

Objectives: Retinoid X receptors (RXRs) are nuclear hormone receptors (NRs) functioning as transcription factors. There are three RXR isoforms: RXRA (NR2B1), RXRB (NR2B2), and RXRG (NR2B3). RXRs serve as master regulators of gene networks governing cell growth, differentiation, survival, and death. RXRs might affect insulin action, but very little data currently supports this relationship. The aim of the study was to analyze the relationship between the expression of RXRs in skeletal muscles and insulin sensitivity in young, normal-weight, overweight and obese people.

Methods: The research group consisted of 45 volunteers, 20 had normal body weight, 13 were overweight, and 12 were obese. Insulin sensitivity was measured with hyperinsulinemic-euglycemic clamp. Vastus lateralis muscle biopsies were taken before each clamp, and RXRs mRNA expression was analyzed.

Results: RXRA expression was lower in overweight, obese subjects in comparison with normal-weight volunteers (P = 0.003, P = 0.002, respectively). RXRB and RXRG expression did not differ between the groups. RXRA expression in muscle was positively correlated with insulin sensitivity (r = 0.49, P = 0.001). The relationship between muscle tissue RXRA and insulin sensitivity was independent of BMI (β = 0.35, P = 0.02).

Conclusions: Our results indicate that RXRA expression in skeletal muscle is linked to insulin sensitivity. The data suggest that muscle-associated RXRs may play a role in modulating insulin action.