Effect of Roux-en-Y gastric bypass surgery on subclinical atherosclerosis, oxidative stress, and mitochondrial dynamics in leukocytes of obese patients: A one-year follow-up study

Abstract

Background and Aims : Little is known about the mechanisms underlying the cardiovascular protective effect of Roux en-Y gastric bypass (RYGB) surgery. The present study aimed to investigate how RYGB influences the oxidative and mitochondrial status of leukocytes and subclinical atherosclerotic markers.Methods: This interventional study was carried out in 57 obese subjects who underwent RYGB surgery. Leukocytes were isolated at baseline and 12 months after the intervention. We evaluated oxidative stress markers by static cytometry and mitochondrial markers by western blot. Leukocyte-endothelial cell interactions - rolling flux, velocity, and adhesion - were evaluated in vitro in a parallel-plate flow chamber.Results: RYGB induced weight loss and an improvement of anthropometric clinical indicators. At the molecular level, a significant reduction of superoxide production (p<0.01) and mitochondrial membrane potential (p<0.05) was observed, while GPX1 content increased (p<0.05). In terms of mitochondria, RYGB induced upregulation of complexes (I-V) (p<0.05 and p<0.001), MIEAP (p<0.05), and Pink1 (p<0.05), and regulated the fusion-fission machinery through an increase in MFN1 (p<0.05). Likewise, a significant reduction of sICAM (p< 0.05) and sP-Selectin (p < 0.001) and of rolling flux (p< 0.05) and adhesion of leukocytes (p< 0.01) were reported at follow-up.Conclusions: Our results suggest that patients undergoing RYGB benefit from an amelioration of their prooxidant status and enhanced mitochondrial dynamics in leukocytes, which could be responsible for the reduction of subclinical markers of atherosclerosis after surgery Acknowledgements: PI19/00838, PI19/00437, FI17/00144, CD19/00180, CP19/00077 from ISCIII-ERDF (“A way to build Europe”), PROMETEO/2019/027; APOSTD/2020/145, ACIF/2020/371 from the Valencian Regional Government. Background and Aims : Little is known about the mechanisms underlying the cardiovascular protective effect of Roux en-Y gastric bypass (RYGB) surgery. The present study aimed to investigate how RYGB influences the oxidative and mitochondrial status of leukocytes and subclinical atherosclerotic markers. Methods: This interventional study was carried out in 57 obese subjects who underwent RYGB surgery. Leukocytes were isolated at baseline and 12 months after the intervention. We evaluated oxidative stress markers by static cytometry and mitochondrial markers by western blot. Leukocyte-endothelial cell interactions - rolling flux, velocity, and adhesion - were evaluated in vitro in a parallel-plate flow chamber. Results: RYGB induced weight loss and an improvement of anthropometric clinical indicators. At the molecular level, a significant reduction of superoxide production (p<0.01) and mitochondrial membrane potential (p<0.05) was observed, while GPX1 content increased (p<0.05). In terms of mitochondria, RYGB induced upregulation of complexes (I-V) (p<0.05 and p<0.001), MIEAP (p<0.05), and Pink1 (p<0.05), and regulated the fusion-fission machinery through an increase in MFN1 (p<0.05). Likewise, a significant reduction of sICAM (p< 0.05) and sP-Selectin (p < 0.001) and of rolling flux (p< 0.05) and adhesion of leukocytes (p< 0.01) were reported at follow-up. Conclusions: Our results suggest that patients undergoing RYGB benefit from an amelioration of their prooxidant status and enhanced mitochondrial dynamics in leukocytes, which could be responsible for the reduction of subclinical markers of atherosclerosis after surgery Acknowledgements: PI19/00838, PI19/00437, FI17/00144, CD19/00180, CP19/00077 from ISCIII-ERDF (“A way to build Europe”), PROMETEO/2019/027; APOSTD/2020/145, ACIF/2020/371 from the Valencian Regional Government.