Involvement of visfatin in palmitate-induced upregulation of inflammatory cytokines in hepatocytes

Metabolism. 2011 Dec;60(12):1781-9. doi: 10.1016/j.metabol.2011.05.003. Epub 2011 Jun 12.

Abstract

Free fatty acids (FFAs) lead to the activation of inflammatory pathways related to the induction of insulin resistance. Visfatin is known to play a role in obesity-related metabolic diseases and inflammatory conditions. Here, the role of visfatin in FFA-induced inflammation was investigated in hepatocytes. The following factors were examined: (1) the protein and messenger RNA (mRNA) expression of visfatin in the liver tissue of insulin-resistant rats and in (2) in HepG2 cells treated with palmitate, (3) the palmitate-induced mRNA expression and protein synthesis of interleukin-6 and tumor necrosis factor-α in HepG2 cells transfected with visfatin-specific small interfering RNA, and (4) the expression of visfatin in HepG2 cells treated with a nuclear factor-κB (NF-κB) inhibitor (SN50) and infected with Ad-IκBα. The protein and mRNA levels of visfatin were significantly higher in insulin-resistant rat liver tissue compared with the control group. Visfatin expression and protein synthesis significantly increased in HepG2 cells treated with palmitate in a time- and concentration-dependent manner. Visfatin-specific small interfering RNA significantly decreased the palmitate-induced mRNA expression and protein synthesis of interleukin-6 and tumor necrosis factor-α. A NF-κB inhibitor induced the downregulation of visfatin in HepG2 cells following treatment with palmitate. HepG2 cells infected with Ad-IκBα showed decreased expression of visfatin following treatment with palmitate. The expression of visfatin is closely associated with the expression of proinflammatory cytokines in FFA-induced inflammation and is significantly decreased by NF-κB inhibition in HepG2 cells. Visfatin may play a role in FFA-induced inflammation in hepatocytes through the NF-κB pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae Infections
  • Animals
  • Blood Glucose / metabolism
  • Cholesterol / blood
  • Cytokines / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Hep G2 Cells
  • Hepatocytes / metabolism*
  • Humans
  • I-kappa B Proteins / metabolism
  • Immunoblotting
  • Inflammation / metabolism*
  • Insulin Resistance
  • Interleukin-6 / blood
  • NF-KappaB Inhibitor alpha
  • Nicotinamide Phosphoribosyltransferase / genetics
  • Nicotinamide Phosphoribosyltransferase / metabolism*
  • Obesity / metabolism*
  • Palmitic Acid / metabolism
  • Peptides / metabolism
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • Rats
  • Rats, Zucker
  • Real-Time Polymerase Chain Reaction
  • Triglycerides / blood
  • Tumor Necrosis Factor-alpha / blood
  • Up-Regulation

Substances

  • Blood Glucose
  • Cytokines
  • I-kappa B Proteins
  • Interleukin-6
  • NFKBIA protein, human
  • Nfkbia protein, rat
  • Peptides
  • RNA, Messenger
  • RNA, Small Interfering
  • SN50 peptide
  • Triglycerides
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha
  • Palmitic Acid
  • Cholesterol
  • Nicotinamide Phosphoribosyltransferase