PULMONARY MYELOPEROXIDASE ACTIVITY AND INSULIN RESISTANCE IN OBESITY

DELLA-VEDOVA, MC; MUNOZ, MD; GARCIA, SILVINA; SANDRA E. GOMEZ-MEJIBA; DARIO C. RAMIREZ

Boston, MA

Congreso; Annual meeting of the SFRBM; 2015

SFRBM

DIO: 10.1016/j.freeradbiomed.2015.10.062In obesity, inflamed adipose tissue releases into circulation anumber of mediators causing insulin resistance (IR) and othermetabolic abnormalities. These mediators are involved inneutrophilic inflammation (NI) in a number of tissues. Activatedneutrophils contain myeloperoxidase (MPO) that produce HOCl.Clorotyrosine is a marker of HOCl protein oxidation. Herein weused a diet-induced obesity (DIO) model that resembles many ofthe features of metabolic syndrome to evaluate NI in the lung andhow it affects peripheral IR. B6 mice were fed for 16 weeks witheither a high-fat diet (HFD, 22% chicken fat) and 10% fructose inthe drinking water (obese mice) or a low-fat diet, 6% chicken fat)and tap water (lean mice). Compared to lean, the obese lung hadmore neutrophils, MPO and markers of protein oxidation(chlorotyrosine and carbonyls) and reduced antioxidant capacity(enzyme activity, GSH, ascorbate). In relation to lean, obeseanimals had more inflammatory and oxidative stress markers inserum; and had more IR. When these animals were instilled dailyfor 7 days before the sacrifice with either 2.5 nmol of DMPO toreduce retention of neutrophils in the lung, 1 nmol of ABAH toinhibit HOCl production by MPO, 5 nmol taurine or 1 nmolresveratrol to scavenge HOCl; we observed reduced lung andsystemic MPO activity, clorotyrosine, oxidative stress/inflammation and peripheral IR compared to non-treated obeseanimals. Conversely, instillation of lean and obese mice with 50uglipopolisaccharide has increased pulmonary MPO, chlorotyrosine,systemic inflammation and were more IR. These data areconsistent with a critical role of neutrophils and MPO-derivedHOCl in worsening IR and systemic inflammation in obesesubjects, especially those exposed to airway irritants PICT-2014-3369 (to DCR), PROICO-2-3214 (To DCR) andPROICO-10-0414(To SEGM).