title: TNF-α downregulates CIDEC via MEK/ERK pathway in human adipocytes.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  TNF-α downregulates CIDEC expression through phosphorylation and nuclear export of PPARγ by MEK/ERK cascade.
authors.affiliation: Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi Province, People's Republic of China.
authors.forename: Xinrui
authors.initials: X
authors.lastname: Tan
authors.affiliation: Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi Province, People's Republic of China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi Province, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi Province, People's Republic of China.
authors.forename: Erdi
authors.initials: E
authors.lastname: Xu
authors.affiliation: Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi Province, People's Republic of China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi Province, People's Republic of China.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Xiao
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins; D016923:Cell Death; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D008066:Lipolysis / Q000502:physiology; D020935:MAP Kinase Signaling System; D009765:Obesity / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D010766:Phosphorylation; D011506:Proteins / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology* / Q000502:physiology
chemical_list: D051017:Apoptosis Regulatory Proteins; C472088:CIDEC protein, human; D047495:PPAR gamma; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha
keywords: CIDEC; TNF-α; lipolysis; obesity