Skeletal muscle expression of the genes associated with glycoprotein 130 signaling in relation to obesity and insulin sensitivity

Glycoprotein 130 (gp130) is a critical signal transducer in the interleukin-6 (IL-6) receptor family, regulates immune response, inflammation, and metabolic processes. In obesity, elevated levels of proinflammatory cytokines like IL-6 can lead to chronic activation of gp130, disrupting normal signaling in tissues such as skeletal muscle. The aim of the study was to investigate the expression of IL-6–related and JAK/STAT pathway genes in human skeletal muscle and to explore their association with insulin sensitivity, as well as to evaluate the role of serum soluble gp130 (sgp130) in the development of overweight and obesity. The study included 57 participants, 25 with normal body weight (control group), 17 with overweight and 15 with obesity. Hyperinsulinemic-euglycemic clamp and muscle biopsy were conducted. Muscle mRNA expression was analysed by qPCR. Individuals with overweight exhibited significantly lower IL6R expression in skeletal muscle, while those with obesity showed reduced IL6ST expression. The expression levels of IL6R (r = 0.28, p = 0.036), IL6ST (r = 0.46, p < 0.001), JAK2 (r = 0.32, p = 0.015), and STAT3 (r = 0.44, p < 0.001) and PRKAA2 (r = 0.26, p = 0.049) in skeletal muscle were positively correlated with insulin sensitivity. Additionally, individuals with overweight and obesity had significantly higher serum sgp130 levels. Serum sgp130 was positively correlated with BMI (r = 0.43, P < 0.01) and inversely associated with insulin sensitivity (r = -0.44, P < 0.01). Gp130 is associated with insulin sensitivity in skeletal muscle in obesity, revealing a novel mechanism linking gp130 to metabolic regulation.