HIGH Nrf2 EXPRESSION DETERMINES LOW METABOLIC RISK: A STUY IN OVERWEIGHT BOYS AND RATS FED A HYPERCALORIC DIET

SANTILLAN, LUCAS; GOMEZ-MEJIBA, SE; GIMENEZ, SOFIA; RAMIREZ, DARIO

Congreso; SAIB 2016; 2016

Excess of energy is metabolized to free fatty acids 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 hypertension, insulin resistance, lipid metabolism, oxidative stress and inflammation. 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 with 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-a, 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 syndrome?s risk. Interventions aimed at increasing expression/activity of Nrf2 may provide a strategy to reduce metabolic risk in overweight/obese patients. PICT-2014-3369 (to DCR)