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（VSG）在治疗肥胖及其并发症方面显示出显著的疗效，但其缓解肥胖及其并发症的分子机制尚不明确。伴随观察到小鼠在VSG术后循环胆汁酸（BAs）水平升高，我们发现VSG术后固醇12α-羟化酶（CYP8B1）的表达下调。通过采用基因修饰的CYP8B1过表达、敲低和敲除小鼠模型，我们证实了VSG改变了胆汁酸的肠肝循环，并通过下调CYP8B1改变了胆汁酸的总体组成。因此，肠道脂质吸收受到限制，肠道微生物群组成亦发生改变，这些变化共同作用于手术的代谢效应。这些研究结果提示，CYP8B1可能是VSG的一个有潜力的靶点，且针对CYP8B1可能成为开发模仿减肥手术以治疗肥胖及其并发症的新疗法的创新策略。