REDUCED NRF2 EXPRESSION INCREASES THE METABOLIC RISK: A STUDY IN OVERWEIGHT BOYS AND RATS FED A HYPERCALORIC DIET

SANTILLAN, LD; RAMIREZ, DC; GIMENEZ, MS ; GOMEZ MEJIBA, SE

MZA

Congreso; SBC; 2016

REDUCED NRF2 EXPRESSION INCREASES THE METABOLIC RISK: A STUDY IN OVERWEIGHT BOYS AND RATS FED A HYPERCALORIC DIET Santillán, LD; Gómez Mejiba, SE; Giménez, MS y Ramirez, DCLaboratory of Experimental and Translational Medicine & Laboratory of Nutrition, Metabolism and Environment. IMIBIO-SL-CCT-San Luis-CONICET-UNSL. San Luis, Argentina. E-mail: ramirezlabimibiosl@ymail.com Excess of energy as free fatty acids that 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 overweight boys (OW, n=22) and normal weight boys (NW, n=27) from San Luis City we measured clinical and biochemical parameters of metabolic syndrome, including hypertension, insulin resistance (IR), lipid metabolism, oxidative stress (OS) and inflammation. Compared to NW, OW boys had IR, higher atherogenic index, altered plasma lipid profile, increased markers of OS and an inflammatory lipid profile. Interestingly, GPx activity and GSH/GSSG ratio and leukocyte?s 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 OS 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 due to increased OS and inflammation. Supported by PICT-2014-3369 (to DCR). Área Temática: Biología Celular y Molecular