OBJECTIVE: Cell death-inducing DFF45-like effector C (CIDEC) is a lipid 
droplet-coating protein that promotes triglyceride accumulation and inhibits 
lipolysis. TNF-α downregulates CIDEC levels to enhance basal lipolysis, whereas 
CIDEC overexpression could block this effect. This study aimed to investigate 
the signaling pathway of TNF-α-mediated CIDEC downregulation in human 
adipocytes.
METHODS: First CIDEC expression was detected in adipose tissue of lean and human 
subjects with obesity. Next, the temporal- and dose-dependent effects of TNF-α 
on CIDEC expression in human SW872 adipocytes were investigated. Selective 
inhibitors or RNAi or constitutively active MEK1 mutant was used to suppress or 
stimulate MEK/ERK cascade. Immunofluorescence and subcellular fractionation 
technique were used to study PPARγ redistribution after TNF-α treatment. 
Reporter assay was performed to confirm the direct effects of TNF-α on CIDEC 
transcription.
RESULTS: CIDEC expression decreased in adipose tissue of subjects with obesity 
and negatively correlated with adipose TNF-α levels and systemic lipolysis. 
TNF-α reduced CIDEC expression in vitro, but suppression of MEK/ERK cascade 
prevented TNF-α-mediated CIDEC downregulation. PPARγ, the transcription factor 
of CIDEC, was phosphorylated and redistributed by TNF-α in a MEK/ERK-dependent 
manner. Reporter assay confirmed that TNF-α reduced CIDEC transcription.
CONCLUSIONS: TNF-α downregulates CIDEC expression through phosphorylation and 
nuclear export of PPARγ by MEK/ERK cascade.