CYP8B1 downregulation mediates the metabolic effects of vertical sleeve gastrectomy in mice.

ABSTRACT:

Background and aims

Although the benefits of vertical sleeve gastrectomy (VSG) surgery are well known, the molecular mechanisms by which VSG alleviates obesity and its complications remain unclear. We aim to determine the role of CYP8B1 (cytochrome P450, family 8, subfamily B, polypeptide 1) in mediating the metabolic benefits of VSG.

Approach and results

We found that expression of CYP8B1, a key enzyme in controlling the 12α-hydroxylated (12α-OH) bile acid (BA) to non-12α-OH BA ratio, was strongly downregulated after VSG. Using genetic mouse models of CYP8B1 overexpression, knockdown, and knockout, we demonstrated that overexpression of CYP8B1 dampened the metabolic improvements associated with VSG. In contrast, short hairpin RNA-mediated CYP8B1 knockdown improved metabolis

SUBMITTER: Liu Y 

PROVIDER: S-EPMC11006827 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature