Bile acid profiles within the enterohepatic circulation in a diabetic rat model after bariatric surgeries
Bile acid profiles within the enterohepatic circulation in a diabetic rat model after bariatric surgeries
复制标题
糖尿病大鼠模型减肥手术后肠肝循环内胆汁酸的分布
DOI：
10.1152/ajpgi.00311.2017
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发表时间：
2018-05-01
影响因子：
4.5
通讯作者：
Hu, San-yuan
中科院分区：
文献类型：
--
作者：
Wei, Meng;Shao, Yi;Hu, San-yuan
胆汁酸（BAs）在肝脏中合成并在肠肝循环中循环，已被认为是通过激活其在肠和肝脏中的受体的信号分子。尽管尚未研究肠肝循环中的术后BA特征，但已证实肥胖手术后血清牛磺酸结合的BA升高。这些配置文件的澄清可能有助于解释减肥手术导致BA配置文件改变和随后的代谢效应的机制。我们施行了空肠-空肠转流术（DJB）、袖状胃切除术（SG）。和假手术在由高脂饮食和链脲佐菌素诱导的肥胖糖尿病大鼠模型中。术后观察体重减轻情况及降糖效果。分析了全身血清和肠肝循环中的BA谱。以及术后12周相关BA转运体和酶的表达。与假手术组相比，SG组体重持续下降，DJB和SO组均显著改善葡萄糖耐量和胰岛素敏感性，并增加胰高血糖素样肽1的分泌。与血清中的变化相似。BAs.特别是牛磺酸结合的物质，在DJB和SG后的肝肠循环（胆汁和门静脉）中也升高。此外，关键的BA转运蛋白和接合酶的表达术后升高，而负责BA合成的酶减少。总之，DJB和SG升高了全身血清和肠肝循环中的BA水平，特别是牛磺酸结合的种类，这可能表明回肠重吸收和肝脏结合增加而不是合成。新&值得注意的是，胆汁酸（BA）被认为是减肥手术的体重无关效应的潜在介质。我们首次发现回肠-空肠旁路和袖状胃切除术升高了BA，特别是肝肠循环中的牛磺酸结合物，可能是通过促进回肠重吸收和肝结合而不是BA合成。这些发现将提高我们对减肥手术后BA代谢及其后续代谢影响的理解。
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 SO 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.