DGAT1 deficiency disrupts lysosome function in enterocytes during dietary fat absorption.

ABSTRACT: Enterocytes, the absorptive cells of the small intestine, mediate the process of dietary fat absorption by secreting triacylglycerol (TAG) into circulation. When levels of dietary fat are high, TAG is stored in cytoplasmic lipid droplets (CLDs) and sequentially hydrolyzed for ultimate secretion. Mice with deficiency in acyl CoA: diacylglycerol acyltransferase 1 (Dgat1-/- mice) were previously reported to have a reduced rate of intestinal TAG secretion and abnormal TAG accumulation in enterocyte CLDs. This unique intestinal phenotype is critical to their resistance to diet-induced obesity; however, the underlying mechanism remains unclear. Emerging evidence shows that lysosomal TAG hydrolysis contributes to autophagy-mediated CLD mobilization termed lipophagy, and when disrupted results in CLD accumulation. In order to study how lipophagy contributes to the unique intestinal phenotype of Dgat1-/- mice, enterocytes from wild-type (WT) and Dgat1-/- mice were examined at 2 and 6?h after oral oil gavage. Through ultrastructural analysis we observed TAG present within autophagic vesicles (AVs) in mouse enterocytes, suggesting the role of lipophagy in intestinal CLD mobilization during dietary fat absorption. Furthermore, we found that Dgat1-/- mice had abnormal TAG accumulation within AVs and less acidic lysosomes compared to WT mice. Together these findings suggest that the delayed dietary fat absorption seen in Dgat1-/- mice is, in part, due to the dysregulated flux of autophagy-mediated CLD mobilization and impairment of lysosomal acidification in enterocytes. The present study highlights the critical role of lysosome in enterocyte CLD mobilization for proper dietary fat absorption.

SUBMITTER: Hung YH 

PROVIDER: S-EPMC7024568 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature