Intestine specific over‐expression of DGAT1 in mice alters triacylglycerol storage in enterocytes, but not body weight in response to a high fat diet

Abstract

Mice deficient in DGAT1 (DGAT1−/−), a key enzyme in triacylglycerol (TG) biosynthesis, are resistant to high fat (HF) diet‐induced obesity (DIO). DGAT1−/− mice have no defect in quantitative absorption of dietary fat; however, their enterocytes store abnormal amounts of TG in cytoplasmic lipid droplets (CLDs). We hypothesized that increased intestine specific‐DGAT1 expression would decrease enterocyte TG storage in CLDs and ultimately result in increased weight gain in response to a HF diet. To test this hypothesis we generated mice with five or twenty fold increased intestine specific DGAT1 over‐expression using the villin promoter (DGAT1IntTG5X and DGAT1IntTG20X). Increasing expression of DGAT1 in the intestine reduced TG storage in CLDs in enterocytes, however, we did not find that DGAT1IntTG5X or DGAT1IntTG20X mice are more susceptible to HF DIO compared to wild‐type mice. These results suggest that intestine specific DGAT1 over‐expression does not affect whole animal energy balance possibly due to high endogenous DGAT1expression in the intestine. This work was supported in part by the PRF and AHA SDG to KKB.