Background

Increased glucagon-like peptide-1 (GLP-1) levels after Roux-en-Y gastric bypass (RYGB) are associated with a larger peripheral blood bile acid (BA) pool, but little is known about the mechanisms and interactions with enterohepatic BA receptor signaling.

Methods

Systemic concentrations of BAs and GLP-1 were quantified at -5, 30, and 180 minutes during an oral meal-tolerance test (MTT) in 6 adults with severe obesity (4 females, aged 29-52 years, BMI 39-62 kg/m2) before and six months after RYGB. Liver mRNA expression of Fxr, Cyp7a1, Cyp8b1, and Cyp27a1 (key enzymes for BA synthesis) was studied in 6 rats with diet-induced obesity before and after RYGB.

Results

Postprandial systemic concentrations of both GLP1 and BAs were blunted during the MTT before RYGB (P>0.05 vs. fasting). After RYGB, BMI decreased 10-17 units, and GLP1 was significantly higher at both 30 and 180 minutes (P<0.05 vs. before RYGB). Post-operative BA concentrations were 2.2-fold higher at 30 minutes (P=0.043) but unchanged at -5 or 180 minutes. Ursodeoxycholate (UDCA) was the only BA species that increased in both fasted and postprandial states and correlated with GLP-1 during the MTT (Spearman’s rho=0.642, P<0.001). Higher UDCA concentrations did not come at the expense of its precursor chenodeoxycholate (CDCA). Accordingly, RYGB increased liver Fxr signaling in rats, as evidenced by downregulated Cyp7a1 and Cyp8b1, while preserved Cyp27a1 suggests a shift from cholate to CDCA and UDCA.

Conclusions

Increased GLP-1 correlates with increased UDCA after RYGB. Redistribution of BAs to the periphery and altered liver synthesis are supported by changes in enterohepatic BA receptor signaling after RYGB.