Enterohepatic Circulation of Bile Acids Is Activated by Bariatric Surgery before Weight Loss Becomes Apparent

Abstract

Bariatric surgery induces metabolic improvement before weight loss occurs. Plasma levels of bile acids (BA) are increased after bariatric surgery and this change is reported to contribute significantly to metabolic improvement. In this study, we investigated rats with duodeno-jejunal bypass (DJB) surgery to assess the mechanism underlying the increase in plasma BA after bariatric surgery, especially before weight loss was detectable. Sprague-Dawley rats were fed a high-fat diet for 10 weeks and then were subjected to DJB surgery. Significant weight loss was noted in the DJB rats from 4 weeks after surgery. However, plasma triglycerides (TG) and the hepatic TG content were reduced at 2 weeks after surgery, although food intake was comparable between DJB rats and sham-operated rats. Plasma levels of total BA were elevated from 2 weeks after DJB surgery. In week 2, plasma levels of cholate and chenodeoxycholate were about 5-fold higher in DJB rats than in sham-operated rats, while cecal levels of both BA were lower in DJB rats compared with sham-operated rats. The increase in plasma BA was suppressed by administration of one of bile acid sequestrants, colestimide. Intestinal expression of BA transporters (ASBT, ABCC3, and OSTα) was up-regulated in DJB rats, and hepatic expression of Cyp7A1 was also up-regulated in DJB rats at 2 weeks after surgery. These findings suggest that activation of de novo biosynthesis and increased enterohepatic circulation of BA contribute to elevation of plasma BA levels after DJB surgery before weight loss becomes apparent. These changes led to alteration of gut microbiota in DJB rats, and the resting core body temperature of DJB rats was increased over that of sham-operated rats from 2 weeks after surgery. Therefore, elevation of plasma BA levels early after bariatric surgery by activation of de novo BA synthesis and enterohepatic circulation may play an important role in postoperative metabolic improvement and weight loss. Disclosure Y. Kitahara: Employee; Self; Ajinomoto Co., Inc. H. Kawanabe: Employee; Self; Ajinomoto Co., Inc. M. Hasumura: Employee; Self; Ajinomoto Co., Inc. Y. Iwai: Employee; Self; Ajinomoto Co., Inc. Y. Okamatsu: Employee; Self; Ajinomoto Co., Inc..