Diacylglycerol acyltransferase 1/2 inhibition induces dysregulation of fatty acid metabolism and leads to intestinal barrier failure and diarrhea in mice.

ABSTRACT: The intestinal metabolism and transport of triacylglycerol (TAG) play a critical role in dietary TAG absorption, and defects in the process are associated with congenital diarrhea. The final reaction in TAG synthesis is catalyzed by diacylglycerol acyltransferase (DGAT1 and DGAT2), which uses activated fatty acids (FA) as substrates. Loss-of-function mutations in DGAT1 cause watery diarrhea in humans, but mechanisms underlying the relationship between altered DGAT activity and diarrhea remain largely unclear. Here, the effects of DGAT1 and DGAT2 inhibition, alone or in combination, on dietary TAG absorption and diarrhea in mice were investigated by using a selective DGAT1 inhibitor (PF-04620110) and DGAT2 inhibitor (PF-06424439). Simultaneous administration of a single dosing of these inhi

SUBMITTER: Takemoto K 

PROVIDER: S-EPMC7422801 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature