Academic Journal

DGAT2 partially compensates for lipid-induced ER stress in human DGAT1-deficient intestinal stem cells[S]

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
الوصف
تدمد:00222275
DOI:10.1194/jlr.M094201