2008-P: Roux-en-Y Gastric Bypass Surgery Can Modulate ER Stress and Inflammation on Subcutaneous Adipose Tissue in Nondiabetic Patients with Obesity

Roux-en-Y gastric bypass (RYGB) is the most effective and durable treatment option for reducing adiposity and control abnormalities of metabolic syndrome in patient with severe obesity. Some studies have shown that the initial effect of RYGB on improving metabolic parameters is due to caloric restriction. However, the impact of RYGB on adipose tissue is still under debate. We evaluated 13 obese, nondiabetic patients (mean age 37 years, 100% women, BMI 42.2 kg/m2) one day before surgery, 3 and 6 months (M) after RYGB. Changes in anthropometric, biochemical e gene expression were evaluated with ANOVA and Pearson’s correlation analysis. BMI, fat mass and blood pressure decreased after 3M and 6M (P≤0.05 for all) compared with baseline. Analysis of gene expression in adipose tissue collected at surgery compared with samples collected at 3M and 6M Post-RYGB showed that interleukins (IL6, TNF-α, and MCP1) and endoplasmic reticulum stress (ERS) genes (EIF2AK3 and CALR) decreased during the follow-up (P≤0.01 for all). Nonetheless, genes involved in energy homeostasis (ADIPOQ and AMPK), cellular response to oxidative stress (SIRT1, SIRT3, and NRF2), regulation of adipogenesis (PPARγ), mitochondrial biogenesis (PGC1α) and amino acid metabolism (GCN2) increased from baseline to all other time points evaluated (P≤0.01 for all). We also observed a strong positive correlation between PGC1α, SIRT1, and AMPK with BMI at 3M (P≤0.01 for all) and ADIPOQ and SIRT1 with BMI at 6M (P≤0.01 for all). Our findings demonstrate that weight loss is associated with amelioration of inflammation and ERS and increased protection against oxidative stress in adipose tissue. These observations are strongly correlated with a decrease in BMI and essential genes that control cellular energy homeostasis, suggesting an adaptive process, in a gene expression level, during the caloric restriction and weight loss period after RYGB in patients without diabetes.