Deficiency of Mitochondrial Glycerol 3-Phosphate Dehydrogenase Contributes to Hepatic Steatosis.
Journal
Hepatology (Baltimore, Md.)
ISSN: 1527-3350
Titre abrégé: Hepatology
Pays: United States
ID NLM: 8302946
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
04
07
2018
accepted:
05
01
2019
pubmed:
18
1
2019
medline:
23
6
2020
entrez:
18
1
2019
Statut:
ppublish
Résumé
Mitochondrial glycerol 3-phosphate dehydrogenase (mGPDH) is an integral component of the respiratory chain, and recent studies have suggested that it plays an important role in hepatic glucose homeostasis. However, its function in hepatic lipid metabolism is unclear. Here, we identified a role for mGPDH in nonalcoholic fatty liver disease (NAFLD). Specifically, mGPDH expression and activity were lower in fatty livers from patients and mice with NAFLD (ob/ob, high-fat diet [HFD] and db/db). Liver-specific depletion of mGPDH in mice or mGPDH knockdown in cultured hepatocytes exacerbated diet-induced triglyceride accumulation and steatosis through enhanced lipogenesis. RNA-sequencing revealed that mGPDH regulated endoplasmic reticulum (ER)-related proteins and processes. mGPDH deletion exacerbated tunicamycin (ER stress inducer)-induced hepatic steatosis, whereas tauroursodeoxycholic acid (ER stress inhibitor) rescued mGPDH depletion-induced steatosis on an HFD. Moreover, ER stress induced by mGPDH depletion could be abrogated by the intracellular Ca
Identifiants
pubmed: 30653687
doi: 10.1002/hep.30507
pmc: PMC6597300
mid: NIHMS1007203
doi:
Substances chimiques
Triglycerides
0
Glycerolphosphate Dehydrogenase
EC 1.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
84-97Subventions
Organisme : Natural Science Foundation Project of Chongqing
ID : cstc2016jcyjA0518
Pays : International
Organisme : National Natural Science Foundation of China
ID : 81471039
Pays : International
Organisme : Natural Science Foundation Project of Chongqing
ID : cstc2016jcyjA0093
Pays : International
Organisme : National Key R&D Program of China
ID : 2017YFC1309602
Pays : International
Organisme : National Key R&D Program of China
ID : 2016YFC1101100
Pays : International
Organisme : Natural Science Foundation Project of Chongqing
ID : cstc2017jcyjA1192
Pays : International
Organisme : American Heart Association
ID : 30970064
Pays : International
Organisme : National Natural Science Foundation of China
ID : 31671222
Pays : International
Organisme : National Natural Science Foundation of China
ID : 81721001
Pays : International
Organisme : National Natural Science Foundation of China
ID : 81600673
Pays : International
Organisme : Natural Science Foundation Project of Chongqing
ID : cstc2014jcyjjq10006
Pays : International
Organisme : NIDDK NIH HHS
ID : R01 DK111436
Pays : United States
Organisme : National Natural Science Foundation of China
ID : 81700714
Pays : International
Organisme : Taishan Scholarship
Pays : International
Organisme : National Natural Science Foundation of China
ID : 81270893
Pays : International
Organisme : NIEHS NIH HHS
ID : R01 ES027544
Pays : United States
Organisme : National Natural Science Foundation of China
ID : 81401601
Pays : International
Organisme : NCI NIH HHS
ID : R21 CA215591
Pays : United States
Informations de copyright
© 2019 by the American Association for the Study of Liver Diseases.
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