title: Involvement of visfatin in palmitate-induced upregulation of inflammatory cytokines in hepatocytes.
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.
authors.affiliation: Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon 443-721, Republic of Korea.
authors.forename: Yong Jun
authors.initials: YJ
authors.lastname: Choi
authors.forename: Sung E
authors.initials: SE
authors.lastname: Choi
authors.forename: Eun Suk
authors.initials: ES
authors.lastname: Ha
authors.forename: Yup
authors.initials: Y
authors.lastname: Kang
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Han
authors.forename: Dae Jung
authors.initials: DJ
authors.lastname: Kim
authors.forename: Kwan Woo
authors.initials: KW
authors.lastname: Lee
authors.forename: Hae Jin
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D000257:Adenoviridae Infections; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D015151:Immunoblotting; D007249:Inflammation / Q000378:metabolism*; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000097:blood; D000072000:NF-KappaB Inhibitor alpha; D054409:Nicotinamide Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D019308:Palmitic Acid / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D060888:Real-Time Polymerase Chain Reaction; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015854:Up-Regulation
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D020672:I-kappa B Proteins; D015850:Interleukin-6; C000606204:NFKBIA protein, human; C000606206:Nfkbia protein, rat; D010455:Peptides; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C118258:SN50 peptide; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D019308:Palmitic Acid; D002784:Cholesterol; D054409:Nicotinamide Phosphoribosyltransferase