c-Jun N-terminal kinase is involved in the suppression of adiponectin expression by TNF-α in 3T3-L1 adipocytes

Abstract

Adiponectin, one of adipokines that is secreted from adipocytes, plays an important role in the regulation of glucose and lipid metabolism. Paradoxically, serum concentrations of adiponectin are decreased in obese and type 2 diabetic patients, although it is produced in adipose tissue. On the other hand, plasma TNF-α levels are increased in such subjects. In the present study, the mechanism by which adiponectin is regulated by TNF-α was investigated. The decreased adiponectin mRNA levels by TNF-α were partially recovered by treatment with a c-Jun N-terminal kinase (JNK) inhibitor or the PPAR-γ agonist rosiglitazone in 3T3-L1 adipocytes. Interestingly, however, cotreatment with the JNK inhibitor and rosiglitazone led to a recovery of TNF-α-mediated adiponectin suppression to the control level. The JNK inhibitor regulated the expression of adiponectin by the increase of PPAR-γ DNA binding activity and the recovery of its mRNA expression while rosiglitazone acted via a PPAR-γ independent pathway which remains to be elucidated. These findings suggest that the JNK signaling pathway, activated by TNF-α, is involved in the regulation of adiponectin expression.