DISRUPTION OF TUMOR NECROSIS FACTORALFA RECEPTOR 1 (TNFR1) SIGNALING PATHWAY INCREASES INTERLEUKIN-1 BETA LEVELS, EXACERBATES HEPATIC INFLAMMATORY RESPONSE AND APOPTOSIS DURING A HIGH FAT DIET (HFD)

LAMBERTUCCI, F; SEDIMEIER, MG; ARBOATTI, A; VILLAR, S; CEBALLOS, MP; ROGGERO, E; ALVAREZ, ML; QUIROGA, AD; CARNOVALE, CE; FRANCES, DEA; RONCO, MT

Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2016

One hallmark of obesity is chronic low grade inflammation andincreased pro-inflammatory circulating cytokines, which play an importantrole in the development of insulin resistance (IR). Obesityassociatedhepatic inflammation is due to increased Kupffer cellactivation and recruited hepatic macrophages. Sustained inflammationmay increase the susceptibility of hepatocytes to apoptoticcell death and therefore exacerbate liver damage. In this work, weaim to study hepatic TNFR1 receptor association with inflammationand apoptosis in a model of IR and altered energy homeostasisinduced by HFD. C57BL/6 wild type (WT) and TNFR1 knock-out(KO) mice (n=6) were fed with regular chow diet (CHOW-WT,CHOW-KO) or a 40% high-fat diet for 16 weeks (HFD-WT, HFDKO).Here, we report that after 16 weeks of HFD, the plasmaticlevels of interleukin(IL)-1β were increased by HFD especially inKO mice (HFD-KO: 189 pg/ml; HFD-WT: 1078 pg/ml; p