title: Liver NF-kappaB and AP-1 DNA binding in obese patients.
abstract: Oxidative stress and insulin resistance (IR) are major contributors in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and in the progression from steatosis to nonalcoholic steatohepatitis (NASH). Our aim was to assess nuclear factor-kappaB (NF-kappaB) and activating protein-1 (AP-1) activation and Toll-like receptor 4 (TLR4) expression as signaling mechanisms related to liver injury in obese NAFLD patients, and examined potential correlations among them, oxidative stress, and IR. Liver NF-kappaB and AP-1 (electromobility shift assay (EMSA)), TLR4 expression (western blot), ferric reducing ability of plasma (FRAP), and IR evolution (HOMA) were evaluated in 17 obese patients who underwent subtotal gastrectomy with gastro-jejunal anastomosis in Roux-en-Y and 10 nonobese subjects who underwent laparoscopic cholecystectomy (controls). Liver NF-kappaB and AP-1 DNA binding were markedly increased in NASH patients (n = 9; P < 0.05) compared to controls, without significant changes in NAFLD patients with steatosis (n = 8), whereas TLR4 expression was comparable between groups. Hepatic NF-kappaB activation was positively correlated with that of AP-1 (r = 0.79; P < 0.0001); both liver NF-kappaB and AP-1 DNA binding were inversely associated with FRAP (r = -0.43 and r = -0.40, respectively; P < 0.05) and directly correlated with HOMA (r = 0.66 and r = 0.62, respectively, P < 0.001). Data presented show enhanced liver activation of the proinflammatory transcription factors NF-kappaB and AP-1 in obese patients with NASH, parameters that are significantly associated to oxidative stress and IR.
authors.affiliation: Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile. lvidela@med.uchile.cl
authors.forename: Luis A
authors.initials: LA
authors.lastname: Videla
authors.forename: Gladys
authors.initials: G
authors.lastname: Tapia
authors.forename: Ramón
authors.initials: R
authors.lastname: Rodrigo
authors.forename: Paulina
authors.initials: P
authors.lastname: Pettinelli
authors.forename: Daniela
authors.initials: D
authors.lastname: Haim
authors.forename: Catherine
authors.initials: C
authors.lastname: Santibañez
authors.forename: A Verónica
authors.initials: AV
authors.lastname: Araya
authors.forename: Gladys
authors.initials: G
authors.lastname: Smok
authors.forename: Attila
authors.initials: A
authors.lastname: Csendes
authors.forename: Luis
authors.initials: L
authors.lastname: Gutierrez
authors.forename: Jorge
authors.initials: J
authors.lastname: Rojas
authors.forename: Jaime
authors.initials: J
authors.lastname: Castillo
authors.forename: Owen
authors.initials: O
authors.lastname: Korn
authors.forename: Fernando
authors.initials: F
authors.lastname: Maluenda
authors.forename: Juan C
authors.initials: JC
authors.lastname: Díaz
authors.forename: Guillermo
authors.initials: G
authors.lastname: Rencoret
authors.forename: Jaime
authors.initials: J
authors.lastname: Poniachik
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002763:Cholecystectomy; D005234:Fatty Liver / Q000209:etiology / Q000601:surgery; D005260:Female; D015390:Gastric Bypass; D005786:Gene Expression Regulation; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D009767:Obesity, Morbid / Q000601:surgery; D018384:Oxidative Stress; D051197:Toll-Like Receptor 4 / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D018808:Transcription Factor AP-1