Context: Adiponectin is a key insulin-sensitising adipokine acting on muscle metabolism via two specific receptors (AdipoR1 and AdipoR2).

Objectives: To investigate the genetic and non-genetic control of plasma adiponectin and muscle AdipoR1/R2 gene expression and the impact of these components on in vivo glucose and fat metabolism.

Design & participants: Plasma adiponectin and muscle gene expression of AdipoR1/R2 were measured before and during insulin infusion in 89 young and 69 elderly monozygotic and dizygotic twins. Insulin action, and glucose and fat oxidation rates were determined using hyperinsulinaemic euglycaemic clamps and indirect calorimetry.

Results: We demonstrated a genetic component in the control of plasma adiponectin and AdipoR1/R2 gene expression. Furthermore, levels of adiponectin and AdipoR1/R2 were influenced by age, sex, abdominal obesity and aerobic capacity. Intra-pair correlations in monozygotic twins indicated a non-genetic influence of birth weight on plasma adiponectin and AdipoR2 expression. Non-oxidative glucose metabolism was associated with AdipoR1 and plasma adiponectin, in young and elderly twins, respectively. In addition, plasma adiponectin was related to glucose and fat oxidation in younger subjects.

Conclusion: Plasma adiponectin and muscle gene expression of its specific receptors are controlled by genetic and several specific non-genetic factors. The data suggest that the "adiponectin axis" plays a role in in vivo insulin action and non-oxidative glucose metabolism.