Nrf2 Expression/activation Determines Metabolic Risk in Obes. 2020.

RAMIREZ DC;GOMEZ-MEJIBA SE. ; MEDAWAR AGUILAR V; CHACON I. DEL V; LUCAS D SANTILLAN; HINOJOSA VERA K; GOMEZ MEJIBA, SANDRA;

GEORGIA

Congreso; Free radical biology and medicine.; 2020

Excess of energy is metabolized to free fatty acids (FFAs) which should be stored as triglycerides (TG) otherwise they cause inflammation, and thus a high risk for obesity-associated abnormalities. Nrf2 controls the expression of phase II/III, antioxidant and adipogenic genes. Low Nrf2 expression may determine inflammation and a high metabolic risk in overweight/obesity. To test this hypothesis, we performed a study in overweight children and in an experimental model of rats fed a hypercaloric diet (HCD). In a population of overweight boys (OW, n=22) and normal weight boys (NW, n=27) from San Luis City we measured clinical and biochemical parameters related to metabolic syndrome, including blood pressure, insulin resistance, lipid metabolism, oxidative stress and inflammation markers. Compared to NW, OW boys had insulin resistance, higher atherogenic index, altered plasma lipid profile, increased markers of oxidative stress and inflammatory lipid profile. Interestingly, GPx activity and GSH/GSSG ratio and leukocyte Nrf2 expression were lower in those OW children at high metabolic risk. Nrf2 expression negatively correlated Dario RamirezVictoria Medawar AguilarInhalenChaconLucasSantillanKathleen HinojosaVeraSandra Gomez-Mejibawith metabolic risk in OW boys. Experimentally we fed male SD rats (n=19) for 16 weeks with a normocaloric (n=7) and HCD (n=12) and found that some rats fed the HCD were obesity sensitive (OS, n=7) whereas the others were obesity resistant (OR, n=5). Compared to OS and in perirenal adipose tissue, OR rats showed a pattern of oxidative stress (increased NOX-2, reduced antioxidant enzymes and increased oxidative stress markers), and inflammation (increased VCAM-1, TNF-α, and lipid profile); but reduced lipogenesis (low Nrf2, PPAR-γ, lipogenic enzyme gene expression, total lipids and TG). Low Nrf2 expression determines reduced adipogenesis but increased metabolic risk. Interventions aimed at increasing Nrf2 expression/activity may provide a strategy to reduce the metabolic risk in overweight/obese patients. PICT-2018-3435 (to DCR)