Roux-en-Y Gastric Bypass Surgery Has Early Differential Effects on Bile Acids and the Levels of Complement Component 3 and Acylation-Stimulating Protein.

Abstract

Bile acids have been implicated in the mechanism by which Roux-en-Y gastric bypass (RYGB) can induce remission of type 2 diabetes (T2D). Our goal was to identify circulating proteins whose levels changed after RYGB when dysglycemic parameters normalized. This was a retrospective study of 26 participants who underwent RYGB. Blood proteins were identified using two-dimensional electrophoresis and mass spectroscopy. Complement proteins were measured using immunoassays and bile acids measured using ultra-high-performance liquid chromatography and mass spectroscopy. A total of 7/452 blood proteins were found to change 2days after RYGB. Complement component 3 (C3) was selected because of its regulation by bile acids and the glucoregulatory function of its proteolytically processed product C3adesArg or acylation-stimulating protein (ASP). The median (inter-quartile range/IQR) C3 level was 47.4 (34.5, 65.9) mg/dL before surgery decreasing to 40.9 (13.4, 64.1) mg/dL within 2days after surgery (p = 0.0292). The median (IQR) ASP level increased from 2.8 (0.9, 7.3) nM before surgery to 8.0 (5.3, 14.1) nM within 2days after surgery (p = 0.0016). ASP levels increased in 14/17 (82%) with T2D remission and in 6/6 with normoglycemia but decreased in 3/3 with persistent T2D. Of ten bile acids measured, the levels of ursodeoxycholic acid (UDCA) were significantly decreased after RYGB and the levels of taurodeoxycholic acid (TDCA) were significantly decreased with T2D remission. These data further support an association of C3 with glucose metabolism and implicate bile acids and ASP in the early remittive effects of RYGB on T2D.