Resveratrol rescues insulin sensitivity in obese adipocytes

DARIO C. RAMIREZ; SANDRA E. GOMEZ-MEJIBA

CABA

Conferencia; VI INTERNATIONAL CONFERENCE ON POLYPHENOLS AND HEALTH; 2013

UBA - SFBM SOUTH AMERICAN CHAPTER

Resveratrol rescues insulin sensitivity in ?obese? adipocytes   Gomez-Mejiba, SE & Ramirez, DC   Laboratory of Experimental Medicine & Therapeutics. IMIBIO-SL-CONICET-UNSL. San Luis, San Luis 5700, Argentina.  E-mail: ramirezlabimibiosl@ymail.com   Resveratrol is a cell permeable trans-stilbene derivative that can scavenge intracellularly produced HOCl (J. Biol. Chem, 285:20062/71). Our DIO model in B6 mice showed that epididimal AT expresses myeloperoxidase (MPO) in AT macrophages (ATM) that also express M1 markers (e.g., IL-6, iNOS). MPO expression was observed in ATM located in the typical crown-like structures; and also inside adipocytes. Tissue fractionation showed MPO mRNA in the ATM, but not in adipocyte fraction. Treatment of these isolated adipocytes with H2O2 blocked glucose uptake. Based on these findings, we hypothesized that MPO interferes with AT insulin signaling by producing HOCl and causing oxidation of intracellular components involved in insulin-triggered signaling.  To test this hypothesis we differentiated human adipocytes and loaded them with human MPO. Treatment of MPO-loaded adipocytes with H2O2 caused intracellular production of HOCl, reduced insulin-triggered GLUT-4 translocation to the membrane and glucose uptake. Furthermore DMPO-based immuno-spin trapping and MS-tandem showed radicalization of specific components of the insulin signaling (e.g., IRS-1/2, SOCS3, GLUT-4). These effects were prevented by resveratrol, but not by taurine or methionine because these cannot pass across the membrane. Together our findings suggest that resveratrol can protect insulin sensitivity in the obese AT by scavenging intracellularly produced HOCl.    Preference: PRESENTACION ORAL