A study of Yanjun et al.

Despite the efficacy of vertical sleeve gastrectomy surgery (VSG), the molecular mechanism by which VSG alleviates obesity and its complications remains unclear. Along with the observation that circulating bile acids (BAs) level is increased after VSG in mice, we found that the expression of sterol 12α-hydroxylase (CYP8B1) is downregulated after VSG. Using the genetically modified CYP8B1-overexpression, knockdown and knockout mouse models, we demonstrate that VSG alters the enterohepatic circulation of BAs and changes the overall BA composition by downregulating CYP8B1. As a consequence, intestinal lipid absorption was restricted, and the gut microbiome composition was shifted as well, which contributes to the metabolic effects of the surgery. These results suggest that CYP8B1 may be a promising target of VSG, and targeting CYP8B1 might be a novel strategy for the development of therapies that mimic bariatric surgery for the treatment of obesity and its complications.尽管垂直袖状胃切除术（vertical sleeve gastrectomy, VSG）已展现出确切疗效，但其缓解肥胖及其并发症的分子机制仍未阐明。结合小鼠接受VSG术后循环胆汁酸（bile acids, BAs）水平升高的观测结果，我们发现术后固醇12α-羟化酶（sterol 12α-hydroxylase, CYP8B1）的表达出现下调。通过构建CYP8B1过表达、敲低及敲除的基因工程小鼠模型，我们证实VSG可通过下调CYP8B1的表达，改变胆汁酸的肠肝循环与整体组成。由此引发的效应包括肠道脂质吸收受到抑制，同时肠道微生物组的组成发生改变，二者共同参与介导该手术的代谢调控作用。上述研究结果表明，CYP8B1或可成为VSG治疗的潜在靶点，而靶向CYP8B1或许可作为开发模拟减重手术疗法的全新策略，用于肥胖及其并发症的治疗。