Chemerin is a newly described adipokine that affects adipogenesis and glucose homeostasis in adipocytes and increases with BMI in humans. This study aimed at investigating the regulation of chemerin release and its effects on glucose metabolism in skeletal muscle cells.

Human skeletal muscle cells were treated with chemerin to study its effects on insulin signalling, glucose uptake and activation of stress kinases. The release of chemerin was analyzed in human adipocytes and adipose tissue explants from lean and obese patients.

Chemerin induces insulin resistance in human skeletal muscle cells at the level of Akt and GSK3 phosphorylation and glucose uptake. Furthermore, chemerin activates p38 MAPK, NF-kB and ERK1/2. Inhibition of ERK partially prevents chemerin-induced insulin resistance pointing to participation of this pathway in chemerin action. Human adipocytes express chemerin and CMKLR1 differentiation-dependently. Fully differentiated fat cells secrete chemerin (15 ng/ml from 10⁶ cells). This process is slightly but significantly increased by TNFa and markedly inhibited by over 80 % by PPARg activation. Adipose tissue explants from obese patients are characterized by significantly higher chemerin secretion as compared to lean controls (21 ng and 8 ng from 10⁷ cells, respectively). Chemerin release is correlated with BMI, waist-hip-ratio and adipocyte volume. Furthermore, higher chemerin release is associated with insulin resistance at the level of lipogenesis and insulin-induced antilipolysis in adipocytes.

Adipocyte-derived secretion of chemerin may be involved in the negative crosstalk between adipose tissue and skeletal muscle contributing to the negative relationship between obesity and insulin sensitivity. A novel role might be assigned to chemerin in glucose and lipid metabolism in both adipose tissue and skeletal muscle.