Differential roles of acyl‐CoA:diacylglycerol acyltransferase1 (DGAT1) and DGAT2 in dietary fat absorption.

Abstract

DGAT1 and DGAT2, are non-homologous enzymes that catalyze the final and rate limiting step in triglyceride (TG) synthesis. DGAT1 and DGAT2 are present in the absorptive cells in the intestine; however, whether DGAT1 and DGAT2 have differential roles in dietary fat absorption is unclear. We studied the roles of DGAT1 and DGAT2 in dietary fat absorption in mice with intestine specific over-expression (DGAT1Int and DGAT2Int). We found similar growth curves and no differences in quantitative dietary fat absorption for DGAT1Int, DGAT2Int, and wild-type (WT) littermates when fed a high fat (HF) diet. We observed TG storage by coherent anti-Stokes Raman scattering microscopy and found consistently less TG storage in enterocytes in DGAT1Int compared to DGAT2Intand WT mice. Postprandial triglyceridemic response was determined in chow fed mice by measuring blood TG concentration before, 1, 2, 3 and 4 h post oral olive oil bolus. Interestingly, AUC was greater for DGAT2Intcompared to DGAT1Intand WT mice. Postprandial TG secretion was determined by blood TG concentration in post i.p. Tyloxapol administration, before, 2 and 4h post oral oil bolus. We observed significant increase in TG secretion rate in DGAT2Intcompared to DGAT1Int and WT mice. Taken together, these results suggest that DGAT1 and DGAT2 have differential roles in dietary fat absorption. Grant Funding Source: American Heart Association