DGAT2 partially compensates for lipid-induced ER stress in human DGAT1-deficient intestinal stem cells.
J Lipid Res
; 60(10): 1787-1800, 2019 10.
Article
en En
| MEDLINE
| ID: mdl-31315900
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Madre
/
Diacilglicerol O-Acetiltransferasa
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Estrés del Retículo Endoplásmico
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Intestinos
/
Lípidos
Límite:
Child, preschool
/
Female
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Humans
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Male
Idioma:
En
Revista:
J Lipid Res
Año:
2019
Tipo del documento:
Article
País de afiliación:
Países Bajos