Endocrine Abstracts

CIDEC is a lipid droplet-targeting protein that promotes triglyceride accumulation and inhibits lipolysis. CIDEC is regulated by peroxisome proliferator-activated receptor γ (PPARγ). Previous studies demonstrate that CIDEC down-regulation is involved in TNFα-induced lipolysis. Here, we focus on the signalling pathway to clarify the mechanism of TNFα-mediated CIDEC down-regulation. CIDEC is significantly decreased in subcutaneous adipose tissue in obese subjects. Also, CIDEC mRNA expression inversely correlates with serum TNFα levels in our cohort of 68 patients. Using SW872 human adipocyte-differentiation model, we verify that TNFα causes lipolysis and CIDEC down-regulation in a dose and time-dependent manner.10 ng/ml TNFα almost abolishes CIDEC protein expression at 12-h exposure, while the MEK/ERK inhibitor U0126, but not the JNK inhibitor SP600125 or the P38 inhibitor SB203580, blocks this response. In addition, RNAi Knockdown of ERK1/2 inhibits TNFα-induced CIDEC down-regulation and phosphorylation of PPARγ. Furthermore, depletion of MEK1/2 which are the upstream activators of ERK1/2 reverse CIDEC down-regulation to a larger extent. Immunostaining of PPARγ and subcellular fractionation confirm that MEK1/2 rather than ERK1/2 mediate PPARγ nuclear exportation. Taken together, TNFα down-regulates CIDEC protein levels due to phosphorylation and nuclear export of PPARγ by MEK/ERK cascade and this adds new aspects of TNFα-induced lipolysis.

Disclosure: This work was supported by National Natural Science Foundation of China No. 81172689.