The nitrone 5,5-dimethyl-1-pyrroline N-oxide improves adipogenesis and reduces insulin resistance in obese mice

INALEN DEL V. CHACON |; FLORENCIA SOLEDAD BARRERA,; CARLA FLORENCIA GUZMAN; DARIO C RAMIREZ; GOMEZ MEJIBA, SANDRA;

ORLANDO-FLORIDA

Congreso; Free Radical Biology And Medicine; 2022

The nitrone spin trap 5,5-dimethyl-1-pyrroline N-oxide(DMPO) enhances the expression of genes under thetranscriptional control of the master regulator of redoxchanges, Nrf-2, such as ggcl, a gene encoding a criticalenzyme involved in glutathione synthesis in macrophages.Nrf2 also controls the expression of two transcriptionfactors (TFs) master regulators of the expression ofadipogenic genes, such as PPAR-y and CEBP-b/a involvedin pre-adipocyte programming/commitment towardadipocytes. These two TFs control the expression ofadipogenic enzymes involved in the synthesis oftriglycerides (TG) from glycerol and free fatty acids(FFAs). If not stored in TG, FFAs cause inflammation andreduce insulin sensitivity. Herein we hypothesized thatDMPO can enhance the adipogenic process, thereforereducing circulating FFA and thus reducing insulinresistance in a mouse model of diet-induced obesity (DIO).DIO cause insulin resistance as assessed by glucose andinsulin tolerance test. DMPO (intratracheal2.5nm/mouse/day) treatment improved insulin sensitivity(GTT and ITT) in obese mice. Our in vitro model showedthat 5mM DMPO added to the differentiation medium(commitment phase) as well in the maintenance mediumdid not change cell viability (MTT assay), but improvedadipogenesis (spectrophotometric measure of TGs usingOil Red O staining). Our data suggest that DMPO improvesinsulin sensitivity in obesity by improving theaccumulation of FFAs in TG. Supported by PICT-2018-03435 and PROICO 022318doi: 10.1016/j.freeradbiomed.2022.10.031