التفاصيل البيبلوغرافية
العنوان: |
DGAT2 partially compensates for lipid-induced ER stress in human DGAT1-deficient intestinal stem cells[S] |
المؤلفون: |
Jorik M. van Rijn, Marliek van Hoesel, Cecilia de Heus, AnkeH.M. van Vugt, Judith Klumperman, EdwardE.S. Nieuwenhuis, RoderickH.J. Houwen, Sabine Middendorp |
المصدر: |
Journal of Lipid Research, Vol 60, Iss 10, Pp 1787-1800 (2019) |
بيانات النشر: |
Elsevier, 2019. |
سنة النشر: |
2019 |
المجموعة: |
LCC:Biochemistry |
مصطلحات موضوعية: |
intestine, triglycerides, diet and dietary lipids, diseases, fatty acid, lipid droplets, Biochemistry, QD415-436 |
الوصف: |
Dietary lipids are taken up as FAs by the intestinal epithelium and converted by diacylglycerol acyltransferase (DGAT) enzymes into triglycerides, which are packaged in chylomicrons or stored in cytoplasmic lipid droplets (LDs). DGAT1-deficient patients suffer from vomiting, diarrhea, and protein losing enteropathy, illustrating the importance of this process to intestinal homeostasis. Previously, we have shown that DGAT1 deficiency causes decreased LD formation and resistance to unsaturated FA lipotoxicity in patient-derived intestinal organoids. However, LD formation was not completely abolished in patient-derived organoids, suggesting the presence of an alternative mechanism for LD formation. Here, we show an unexpected role for DGAT2 in lipid metabolism, as DGAT2 partially compensates for LD formation and lipotoxicity in DGAT1-deficient intestinal stem cells. Furthermore, we show that (un)saturated FA-induced lipotoxicity is mediated by ER stress. More importantly, we demonstrate that overexpression of DGAT2 fully compensates for the loss of DGAT1 in organoids, indicating that induced DGAT2 expression in patient cells may serve as a therapeutic target in the future. |
نوع الوثيقة: |
article |
وصف الملف: |
electronic resource |
اللغة: |
English |
تدمد: |
0022-2275 |
Relation: |
http://www.sciencedirect.com/science/article/pii/S0022227520323105; https://doaj.org/toc/0022-2275 |
DOI: |
10.1194/jlr.M094201 |
URL الوصول: |
https://doaj.org/article/87eadb94c84e4ebbb7137284c417f471 |
رقم الانضمام: |
edsdoj.87eadb94c84e4ebbb7137284c417f471 |
قاعدة البيانات: |
Directory of Open Access Journals |