Effect of Roux-en-Y Gastric Bypass on circulating oxylipin profile in women with obesity and type 2 diabetes

Background & Aims: Chronic inflammation associated with obesity directly contributes to metabolic comorbidities, including type 2 diabetes (T2D). Roux-en-Y gastric bypass (RYGB) is a highly effective treatment for obesity-associated T2D. We investigated the effect of RYGB on the circulating profile of oxylipins derived from arachidonic (ARA), eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids as a potential mechanism underlying the metabolic benefits of the surgery. Methods: Plasma samples were collected from 28 women with obesity and T2D before and 3 months after RYGB. Circulating levels of oxylipins and their precursors, along with biochemical markers of glucose homeostasis, were evaluated using untargeted mass spectrometry and routine biochemical techniques, respectively. Results: No significant changes were observed in the levels of oxylipins derived from EPA and DHA. However, there was an increase in ARA and its derived oxylipins, TXB2 (an inert derivative of TXA2) and PGD2 (Wilcoxon, p ≤ 0.05). Positive correlations were observed between hemoglobin A1c levels and TXB2 as well as ARA levels (Spearman, p ≤ 0.05). Conclusions: Our data suggest that the anti-inflammatory oxylipins derived from EPA and DHA may not be involved in the metabolic benefits associated with RYGB. However, the findings indicate that the pro-inflammatory oxylipin TXA2 and its precursor ARA may negatively impact glucose homeostasis both before and after RYGB.