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Liver NF‐κB and AP‐1 DNA Binding in Obese Patients
Author(s) -
Videla Luis A.,
Tapia Gladys,
Rodrigo Ramón,
Pettinelli Paulina,
Haim Daniela,
Santibañez Catherine,
Araya A. Verónica,
Smok Gladys,
Csendes Attila,
Gutierrez Luis,
Rojas Jorge,
Castillo Jaime,
Korn Owen,
Maluenda Fernando,
Díaz Juan C.,
Rencoret Guillermo,
Poniachik Jaime
Publication year - 2009
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1038/oby.2008.601
Subject(s) - nonalcoholic fatty liver disease , medicine , steatosis , proinflammatory cytokine , oxidative stress , endocrinology , fatty liver , tlr4 , insulin resistance , inflammation , obesity , disease
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‐κB (NF‐κB) 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‐κB 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‐κB 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‐κB activation was positively correlated with that of AP‐1 ( r = 0.79; P < 0.0001); both liver NF‐κB 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‐κB and AP‐1 in obese patients with NASH, parameters that are significantly associated to oxidative stress and IR.