247-OR: Positive Effects of Bariatric Surgery Are Associated with Attenuation of Cellular Senescence

Bariatric surgery represents the most efficient approach to treatment of obesity; however, the detailed mechanism of its positive metabolic effect is still not fully understood. Cellular senescence arrests the cell cycle in damaged cells thus preventing further spreading of the damage. Persistence of senescent cells especially in adipose tissue can, however, contribute to the development of a number of chronic diseases including obesity and its complications. Reduction of adipose tissue after bariatric surgery can therefore reduce the number of senescent cells and their negative effects on organism. 17 patients with obesity (2nd grade and higher) scheduled for bariatric surgery (sleeve gastrectomy) were included into the study. Subcutaneous (SAT) adipose tissue and plasma were collected during and 6 months after surgery. The analysis of samples included RT-qPCR (mRNA transcription in SAT) and ELISA or Luminex for detection of hormones and proteins from plasma. Our results show that bariatric surgery reduces the amount of senescent cells in adipose tissue, which results in the decrease of oxidative stress and inflammation, partially also by reduced recruitment of pro-inflammatory macrophages. In addition, we detected lower plasma levels of soluble E-selectin and ICAM-1, molecules enhancing cardiovascular damage known to be produced by senescent cells, as well as decreased expression of ACE2, whose increased expression was detected in senescent cells. Importantly, we also observed decreased expression of ADAM17 responsible for producing a soluble form of ACE2, a newly identified predictor of cardiovascular damage. In conclusion, reduction of senescent cells in adipose tissue after bariatric surgery contributes to improvement of inflammation and metabolic parameters in patients with obesity and decreases the risk of cardiovascular complications. Disclosure S.Stemberkova hubackova: None. T.Havrlantova: None. I.Simonik: None. M.Mraz: None. M.Haluzik: Advisory Panel; Novo Nordisk, Lilly Diabetes, Boehringer-Ingelheim, Research Support; Sanofi, Speaker's Bureau; Abbott, AstraZeneca. Funding Czech Health Science Foundation (NU22-01-00096); Programme EXCELES (LX22NPO5104); Czech Ministry of Health (IKEM, IN00023001)