Pulmonary Mieloperoxidase Activity Worsen Insulin Resistance in Obese Mice Exposed to Bacterial Endotoxin.

DELLA VEDOVA, M.C ; M.C; MUÑOZ, M.D. ; SANTILLAN, LD. ; GARCÍA, S.; GÓMEZ, N.N. ; SUSANA E SIEWERT; SAURABH CHATTERJEE; SANDRA E GOMEZ MEJIBA; DARIO C RAMIREZ

Congreso; SFRBM; 2016

doi: 10.1016/j.freeradbiomed.2016.10.452 Pulmonary Myeloperoxidase Activity Worsens InsulinResistance in Obese Mice Exposed to BacterialEndotoxinMaria C Della Vedova1, Marcos D Munoz1, Ernesto R Verni1, SilvinaGarcia1, Susana E Siewert1, Nidia N Gomez1, Saurabh Chatterjee2,Sandra E Gomez Mejiba1, and Dario C Ramirez11CONICET-UNSL, San Luis, Argentina, 2Environmental Health &Disease Laboratory, University of South Carolina, Columbia, USANeutrophilic inflammation (NI) is a poorly known process occurringin the lung of obese subjects exposed to indoor airborne pollutantsthat may worsen many obesity-associated metabolicabnormalities, including insulin resistance (IR). Indeed, obesepatients exposed to indoor-airborne pollutants show worse IR thanthose unexposed, however the reasons for this disparity arepartially known. Bacterial lipopolysaccharide (LPS) is a stressorthat when administrated by intratracheal instillation (ITI) causes NIin the lung. At sites of NI, myeloperoxidase (MPO) oxidizes chlorideanions to hypochlorous acid/hypochlorite (HOCl/OCl) which candamage the lung, increase systemic oxidative stress/inflammationand thus worsen IR. Hydrazide 4-aminobenzoic acid (ABAH) is afairly-specific inhibitor of MPO. Taurine is a non-cell-permeablescavenger of HOCl. Herein we hypothesized that inhibition ofoxidative processes mediated by MPO in the obese lung canreduce IR in obesity. To test this hypothesis we used male B6 micewhich were fed a high-chicken-fat diet and fructose (obese) and alow-fat diet and tap-water (control). During the last week of diet andon a daily basis both groups of mice were ITI with either PBS(vehicle), ABAH (10 µmol/mouse) or taurine (5nmol/mouse). Thelast day-of-treatment animals were ITI with 2.5 µg LPS/mouse orPBS alone; and 6 h later an intraperitoneal glucose tolerance testwas performed. A total of 6 groups, for both control and obesemice, were compared (PBS, LPS, ABAH, ABAH+LPS, Tau andTau+LPS). Compared to control, LPS treatment to obese miceincreased more lung MPO activity, chlorotyrosine, nitrotyrosine,TNF-α; but reduced insulin sensitivity. These differences betweencontrol and obese mice upon treatment with LPS were abrogatedwhen animals were pre-treated with either ABAH or taurine. Weconclude that MPO-driven oxidative modifications in the lung ofobese animals are responsible for worsening IR when and mayprovide a therapeutic target to reduce IR in obese subjectsexposed to indoor-airborne pollutants.Supported by PROICO 2-3214 & PICT-2014-3369 (to DCR),PROICO 10-0414 (To SEGM) and PIP2015-2017-112215-0100603CO (To DCR, SEA & SEGM).doi: 10.1016/j.freeradbiomed.2016.10.452