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.