Department of General Surgery, Qilu Hospital of Shandong University , Jinan , People's Republic of China.
Am J Physiol Gastrointest Liver Physiol. 2018 May 1;314(5):G537-G546. doi: 10.1152/ajpgi.00311.2017. Epub 2017 Dec 21.
Bile acids (BAs), which are synthesized in the liver and cycled in the enterohepatic circulation, have been recognized as signaling molecules by activating their receptors in the intestine and liver. Serum taurine-conjugated BAs have been shown to be elevated after bariatric surgeries although the postoperative BA profiles within the enterohepatic circulation have not been investigated. Clarification of these profiles could help explain the mechanisms by which bariatric surgery leads to BA profile alterations and subsequent metabolic effects. We performed duodenal-jejunal bypass (DJB), sleeve gastrectomy (SG), and sham procedures in an obese diabetic rat model induced by high-fat diet and streptozotocin. The weight loss and antidiabetic effects were evaluated postsurgery. BA profiles in the systemic serum and within the enterohepatic circulation were analyzed, together with the expression of related BA transporters and enzymes at week 12 after surgery. Compared with sham, SG induced sustained weight loss, and both DJB and SG significantly improved glucose tolerance and insulin sensitivity with enhanced glucagon-like peptide 1 secretion. Similar to changes in the serum, BAs, especially taurine-conjugated species, were also elevated in the enterohepatic circulation (bile and portal vein) after DJB and SG. In addition, the expression of key BA transporters and conjugational enzymes was elevated postoperatively, whereas the enzymes responsible for BA synthesis were decreased. In conclusion, DJB and SG elevated BA levels in the systemic serum and enterohepatic circulation, especially taurine-conjugated species, which likely indicates increased ileal reabsorption and hepatic conjugation rather than synthesis. NEW & NOTEWORTHY Bile acids (BAs) have been implicated as potential mediators of the weight-independent effects of bariatric surgery. For the first time, we discovered that duodenal-jejunal bypass and sleeve gastrectomy elevated BAs, particularly the taurine-conjugated species in the enterohepatic circulation, likely through the promotion of ileal reabsorption and hepatic conjugation rather than BA synthesis. These findings will improve our understanding of BA metabolism after bariatric surgery and their subsequent metabolic effects.
胆汁酸（BAs）在肝脏中合成并在肠肝循环中循环，通过在肠道和肝脏中激活其受体，已被认为是信号分子。尽管尚未研究术后肠肝循环中的 BA 谱，但已经表明肥胖手术后血清牛磺酸结合的 BAs 水平升高。阐明这些谱有助于解释减肥手术后 BA 谱改变和随后的代谢效应的机制。我们在高脂肪饮食和链脲佐菌素诱导的肥胖糖尿病大鼠模型中进行了十二指肠空肠旁路（DJB）、胃袖状切除术（SG）和假手术。术后评估体重减轻和抗糖尿病作用。分析了手术后第 12 周时系统血清和肠肝循环中的 BA 谱，以及相关 BA 转运体和酶的表达。与假手术相比，SG 诱导持续的体重减轻，DJB 和 SG 均显著改善葡萄糖耐量和胰岛素敏感性，同时增强胰高血糖素样肽 1 分泌。与血清中的变化相似，BAs，特别是牛磺酸结合的物种，在 DJB 和 SG 后也在肠肝循环（胆汁和门静脉）中升高。此外，手术后关键 BA 转运体和结合酶的表达升高，而负责 BA 合成的酶减少。总之，DJB 和 SG 增加了系统血清和肠肝循环中的 BA 水平，特别是牛磺酸结合的物种，这可能表明回肠吸收和肝结合增加，而不是合成增加。
新的和值得注意的是，胆汁酸（BAs）被认为是减肥手术的体重独立作用的潜在介质。我们首次发现十二指肠空肠旁路和胃袖状切除术增加了肠肝循环中的 BA，特别是牛磺酸结合的物种，这可能是通过促进回肠吸收和肝脏结合而不是 BA 合成。这些发现将提高我们对减肥手术后 BA 代谢及其随后的代谢效应的理解。
