Loss of function of transcription factor EB remodels lipid metabolism and cell death pathways in the cardiomyocyte.
Animals
Apoptosis
/ physiology
Autophagy
/ drug effects
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
/ genetics
Cell Death
/ physiology
Cell Nucleus
Gene Expression Regulation
Kruppel-Like Transcription Factors
/ metabolism
Lipid Metabolism
/ physiology
Lysosomes
/ metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Myocytes, Cardiac
/ metabolism
Obesity
/ metabolism
Signal Transduction
/ physiology
Transcriptome
Autophagy
Cardiomyocyte apoptosis
Lysosome
Metabolism
Obesity
TFEB
Journal
Biochimica et biophysica acta. Molecular basis of disease
ISSN: 1879-260X
Titre abrégé: Biochim Biophys Acta Mol Basis Dis
Pays: Netherlands
ID NLM: 101731730
Informations de publication
Date de publication:
01 10 2020
01 10 2020
Historique:
received:
18
12
2019
revised:
24
04
2020
accepted:
27
04
2020
pubmed:
22
5
2020
medline:
15
12
2020
entrez:
22
5
2020
Statut:
ppublish
Résumé
Glucolipotoxicity following nutrient overload causes cardiomyocyte injury by inhibiting TFEB and suppressing lysosomal function. We ascertained whether in addition to the amount, the type of fatty acids (FAs) and duration of FA exposure regulate TFEB action and dictate cardiomyocyte viability. Saturated FA, palmitate, but not polyunsaturated FAs decreased TFEB content in a concentration- and time-dependent manner in cardiomyocytes. Hearts from high-fat high-sucrose diet-fed mice exhibited a temporal decline in nuclear TFEB content with marked elevation of diacylglycerol and triacylglycerol, suggesting that lipid deposition and TFEB loss are concomitant molecular events. Next, we examined the identity of signaling and metabolic pathways engaged by the loss of TFEB action in the cardiomyocyte. Transcriptome analysis in murine cardiomyocytes with targeted deletion of myocyte TFEB (TFEB
Identifiants
pubmed: 32437957
pii: S0925-4439(20)30177-0
doi: 10.1016/j.bbadis.2020.165832
pii:
doi:
Substances chimiques
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
0
Klf15 protein, mouse
0
Kruppel-Like Transcription Factors
0
Tcfeb protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
165832Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.