Deficiency of intestinal Bmal1 prevents obesity induced by high-fat feeding.

ABSTRACT: The role of intestine clock in energy homeostasis remains elusive. Here we show that mice with Bmal1 specifically deleted in the intestine (Bmal1^iKO mice) have a normal phenotype on a chow diet. However, on a high-fat diet (HFD), Bmal1^iKO mice are protected against development of obesity and related abnormalities such as hyperlipidemia and fatty livers. These metabolic phenotypes are attributed to impaired lipid resynthesis in the intestine and reduced fat secretion. Consistently, wild-type mice fed a HFD during nighttime (with a lower BMAL1 expression) show alleviated obesity compared to mice fed ad libitum. Mechanistic studies uncover that BMAL1 transactivates the Dgat2 gene (encoding the triacylglycerol synthesis enzyme DGAT2) via direct binding to an E-box in the

SUBMITTER: Yu F 

PROVIDER: S-EPMC8423749 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature