ROLE OF TUMOR NECROSIS FACTOR-ALPHA RECEPTOR 1 (TNFR1) SIGNALING PATHWAY IN THE PROGRESSION OF HEPATIC STEATOSIS AND LIVER DAMAGE

FLAVIA LAMBERTUCCCI; AINELEN ARBOATTI; JUAN A. MONTI; GERARDO B. PISANI; ARIEL D. QUIROGA; CARNOVALE, CRISTINA E; DANIEL E. FRANCÉS; RONCO MARIA TERESA

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

In obese individuals, the excess fat accumulates in the liver andit is associated with hepatic low grade inflammation. Pro-inflammatorycytokines as TNF-a, IL-6 or IL-1β promote sustained inflammationthat increase the susceptibility of hepatocytes to apoptoticcell death and therefore exacerbate liver damage. We evaluated theeffects of high caloric feeding on the phenotype of TNFR1 knockoutmice to assess its role in the progression of steatohepatitis,apoptosis and liver damage. C57BL/6J wild type (WT) and knockoutC57BL/6-Tnfrsf1atm1Imx/J (TNFR1 KO) mice (n=6) were fedwith regular chow diet (CHOW) or a 40% high-fat diet (HFD) for16 weeks. Liver pro-inflammatory cytokines mRNA was increase inHFD-KO compared with HFD-WT (RT-PCR; IL-1β: 6-fold increase;TNFa: 2-fold increase; IL-6: 4-fold increase), but only plasmaticIL-1β levels showed a statistically significant increase in HFD-KOmice (ELISA; HFD-WT: 189 pg/ml; HFD-KO: 1078 pg/ml). In linewith this, liver immunoblot membrane expression of its receptor wasincreased in HFD-KO (+40%) vs HFD-WT (p