Human skeletal muscle releases leptin in vivo

► Muscle biopsies indicated that human skeletal muscle synthesizes leptin. ► Skeletal muscle released leptin in vivo. ► Leptin release from adipose tissue did not respond to adrenaline infusion. ► Leptin release from skeletal muscle was suppressed during adrenaline infusion. Leptin is considered an adipokine, however, cultured myocytes have also been found to release leptin. Therefore, as proof-of-concept we investigated if human skeletal muscle synthesized leptin by measuring leptin in skeletal muscle biopsies. Following this, we quantified human skeletal muscle and adipose tissue leptin release in vivo. We recruited 16 healthy male human participants. Catheters were inserted into the femoral artery and vein draining skeletal muscle, as well as an epigastric vein draining the abdominal subcutaneous adipose tissue. By combining the veno-arterial differences in plasma leptin with measurements of blood flow, leptin release from both tissues was quantified. To induce changes in leptin, the participants were infused with either saline or adrenaline in normo-physiological concentrations. The presence of leptin in skeletal muscle was confirmed by western blotting. Leptin was released from leg skeletal muscle (50.6±12ngmin−1) and the pattern of release was different from subcutaneous adipose tissue. Moreover, during adrenaline infusion the leptin release from leg skeletal muscle was strongly suppressed (20.5±7.9ngmin−1, p