IMIBIO-SL   20937
INSTITUTO MULTIDISCIPLINARIO DE INVESTIGACIONES BIOLOGICAS DE SAN LUIS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
PULMONARY MYELOPEROXIDASE ACTIVITY AND INSULIN RESISTANCE IN OBESITY
Autor/es:
DELLA VEDOVA, MC, MUÑOZ, MD, ; GARCÍA, S,; GOMEZ-MEJIBA, SE Y RAMIREZ, DC.
Reunión:
Congreso; Sociedad de Radicales Libres; 2015
Institución organizadora:
FREE RADICALS AND BIOLOGY MEDICINE
Resumen:
In obesity, inflamed adipose tissue releases into circulation a number of mediators causing insulin resistance (IR) and other metabolic abnormalities. These mediators are involved in neutrophilic inflammation (NI) in a number of tissues. Activated neutrophils contain myeloperoxidase (MPO) that produce HOCl. Clorotyrosine is a marker of HOCl protein oxidation. Herein we used a diet-induced obesity (DIO) model that resembles many of the features of metabolic syndrome to evaluate NI in the lung and how it affects peripheral IR. B6 mice were fed for 16 weeks with either a high-fat diet (HFD, 22% chicken fat) and 10% fructose in the drinking water (obese mice) or a low-fat diet, 6% chicken fat) and tap water (lean mice). Compared to lean, the obese lung had more neutrophils, MPO and markers of protein oxidation (chlorotyrosine and carbonyls) and reduced antioxidant capacity (enzyme activity, GSH, ascorbate). In relation to lean, obese animals had more inflammatory and oxidative stress markers in serum; and had more IR. When these animals were instilled daily for 7 days before the sacrifice with either 2.5 nmol of DMPO²to reduce retention of neutrophilsin the lung, 1 nmol of ABAH²to inhibit HOCl production by MPO, 5 nmol taurine or 1 nmol resveratrol²to scavenge HOCl; we observed reduced lung and systemic MPO activity, clorotyrosine, oxidative stress/ inflammation and peripheral IR compared to non-treated obese animals. Conversely, instillation of lean and obese mice with 50Pg lipopolisaccharide has increased pulmonary MPO, chlorotyrosine, systemic inflammation and were more IR. These data are consistent with a critical role of neutrophils and MPO-derived HOCl in worsening IR and systemic inflammation in obese subjects, eVSHFLDOOWKRVHH[SRVHGWRDLUZDV¶LUULWDQWVPICT-2014-3369 (to DCR), PROICO-2-3214 (To DCR) and PROICO10-0414(To SEGM)