MYELOPEROXIDASE AND ADIPOKINE SWITCH IN ADIPOCYTES.

GOMEZ-MEJIBA S.E; RAMIREZ D,

SAN LUIS

Congreso; LIBRO DE RESÚMENES XXX REUNIÓN CIENTÍFICA ANUAL DE LA SOCIEDAD DE BIOLOGÍA DE CUYO,; 2012

SOCIEDAD DE BIOLOGÍA DE CUYO,

MYELOPEROXIDASE AND ADIPOKINE SWITCH IN ADIPOCYTES.(POSTER) Gomez-Mejiba SE, Ramirez DC. Lab de Medicina Experimental y Terapéutica. IMIBIO-SL-CONICETUNSL. 5700 San Luis. In the normal adipose tissue (AT), adipocytes secrete more adiponetin (Ad) than leptin (Lp); however, in obesity they secrete more Lp than Ad. The molecular bases of this adipokines switch are unclear. Our in vivo mouse model of diet-induced obesity has shown that AT is infiltrated with macrophages that express and release myeloperoxidase (MPO) that is taken up by adipocytes. We hypothesized that oxidations promoted by HOCl, produced inside adipocytes, cause this switch towards inflammation. To test this hypothesis we used adipocytes loaded with MPO and stressed them with H2O2 to produce HOCl inside the cell. We observed no changes in cell viability, but Lp secretion increased and Ad secretion was reduced. This switch was prevented by the MPO inhibitor ABAH or resveratrol?a cell permeable scavenger of HOCl. HOCl generated inside the adipocyte produce oxidation and aggregation of Ad in the endoplasmic reticulum (ER) and caused ER stress. Intracellular production of HOCl also increased Lp secretion by adipocytes. Immuno-spin trapping showed that Ad and prolyl hydroxylase-2 (PHD-2) were two of the major targets of oxidation in the adipocyte. Like resveratrol, DMPO re-established the normal pattern of secretion of adipokines, prevented HIF-1 increase and ameliorated ER stress. The decreased secretion of Ad was related to increased retention of oxidized Ad in the ER, whereas increased Lp secretion might be due to increased HIF-1 stability, likely due to PHD-2 inhibition. These results highlight an important role of the synthesis and secretion of MPO by macrophages in the obese AT and adipokine switch in adipocytes.