Department of Surgery, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1, Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
Obes Surg. 2020 Jul;30(7):2528-2537. doi: 10.1007/s11695-020-04506-3.
Bile acids (BAs) are important in the metabolic effects of bariatric surgery. Most BAs are reabsorbed in the ileum and recycled back to the liver. We have reported that this enterohepatic circulation was shortened by duodenal-jejunal bypass (DJB), and the biliopancreatic (BP)-limb plays an important role in reabsorption of BAs. However, the mechanism of BA reabsorption in BP-limb remains uncertain. We aimed to investigate the mechanisms of BA reabsorption after DJB, especially focusing on carrier-mediated transport of BAs and the impact of the presence or absence of lipids on BA reabsorption.
Otsuka-Long-Evans-Tokushima fatty rats or Sprague-Dawley rats were assigned to a control group and DJB group. BA levels in the divided small intestine were quantified with liquid chromatography-mass spectrometry. Labeled BA was injected and perfused with BA transporter inhibitors or mixture of lipids in the isolated BP-limb, and bile was sampled and analyzed.
Conjugated BA levels in the BP-limb were significantly higher than that of the control group. BA absorption tended to decrease by the apical sodium-dependent BA transporter inhibitor and was significantly decreased by the organic anion-transporting peptide (OATP) inhibitor. BA absorption tended to increase in the absence of lipid solutions compared with that in the presence of lipid solutions.
We attributed the increased BA reabsorption in the BP-limb to lack of food in the BP-limb, which contains concentrated BAs and no lipids. OATP played an important role in BA reabsorption in the BP-limb. Therefore, BAs would be reabsorbed in different manners after DJB.
胆汁酸(BAs)在减重手术的代谢作用中很重要。大多数胆汁酸在回肠中被重吸收并循环回肝脏。我们曾报道过,十二指肠空肠旁路术(DJB)缩短了这种肠肝循环,而胆胰(BP)支在胆汁酸的重吸收中起着重要作用。然而,BP 支中胆汁酸重吸收的机制仍不清楚。我们旨在研究 DJB 后胆汁酸重吸收的机制,特别是关注胆汁酸的载体介导转运以及脂质的存在与否对胆汁酸重吸收的影响。
将 Otsuka-Long-Evans-Tokushima 肥胖大鼠或 Sprague-Dawley 大鼠分为对照组和 DJB 组。采用液相色谱-质谱法对分段小肠中的胆汁酸水平进行定量。在分离的 BP 支中用 BA 转运体抑制剂或脂质混合物注射和灌注标记的 BA,并取样和分析胆汁。
BP 支中的结合胆汁酸水平明显高于对照组。顶端钠依赖性胆汁酸转运体抑制剂使胆汁酸吸收倾向于减少,而有机阴离子转运肽(OATP)抑制剂使胆汁酸吸收显著减少。与存在脂质溶液相比,无脂质溶液中胆汁酸吸收倾向于增加。
我们认为 BP 支中胆汁酸重吸收增加是由于 BP 支中缺乏食物,BP 支中含有浓缩的胆汁酸而没有脂质。OATP 在 BP 支中胆汁酸重吸收中起着重要作用。因此,DJB 后胆汁酸会以不同的方式被重吸收。