title: TNF-alpha and IL-6 inhibit apolipoprotein A-IV production induced by linoleic acid in human intestinal Caco2 cells.
abstract: BACKGROUND
  Apolipoprotein A-IV (apoA-IV) is a protein mainly synthesized by enterocytes in the intestine. Its gene expression is suppressed during fasting and stimulated during active fat absorption. Chronic feeding of a high-fat (HF) diet abolishes the differential expression between fasting and fat-feeding and therefore may contribute to diet-induced obesity since apoA-IV is a potent satiety factor. It is well established that the circulating pro-inflammatory cytokines TNF-α and IL-6 are increased by HF feeding.
  
  
  METHODS
  To determine whether pro-inflammatory cytokines are involved in the diminished response of apoA-IV gene expression to fat-feeding, different concentrations of linoleic acid (LA), an important dietary fatty acid, was used to stimulate apoA-IV expression in human intestinal Caco2 cells. Cells were pre-treated with or without human recombinant TNF-α, IL-6 or their combination before the addition of LA. Real-time PCR and ELISA were used to detect and quantify RNA transcripts and proteins of apoA-IV and the cytokines.
  
  
  RESULTS
  LA stimulated gene and protein expression of apoA-IV in a dose and time dependent manner. Pre-treatment with the cytokines for 72 h significantly inhibited the increased expression of apoA-IV gene and protein induced by LA. Furthermore, the cytokines, especially TNF-α, also positively up-regulate the cytokine themselves in Caco2 cells.
  
  
  CONCLUSIONS
  Our data indicate that the pro-inflammatory cytokines may be responsible for the reduced apoA-IV production in response to fat feeding. Because of apoA-IV's role in satiety, we propose the inhibitory effect of circulating pro-inflammatory cytokines on apoA-IV production contributes to diet-induced obesity.
authors: National Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, 710004 China ; Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, 45237-0507 USA.
authors: Xiaoming
authors: X
authors: Li
authors: Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, 45237-0507 USA.
authors: Min
authors: M
authors: Xu
authors: Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, 45237-0507 USA.
authors: Min
authors: M
authors: Liu
authors: Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, 45237-0507 USA.
authors: Yong
authors: Y
authors: Ji
authors: National Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, 710004 China.
authors: Zongfang
authors: Z
authors: Li
keywords: Apolipoprotein A-IV; Fatty acid; IL-6; Linoleic acid; TNF-α