Thioesterase superfamily member 2 promotes hepatic insulin resistance in the setting of glycerol-3-phosphate acyltransferase 1-induced steatosis.
diacylglycerol
fatty acid
fatty acid metabolism
insulin resistance
liver
triacylglycerol
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
08 02 2019
08 02 2019
Historique:
received:
02
08
2018
revised:
21
11
2018
pubmed:
14
12
2018
medline:
14
5
2019
entrez:
8
12
2018
Statut:
ppublish
Résumé
Hepatic insulin resistance in the setting of steatosis is attributable at least in part to the accumulation of bioactive lipids that suppress insulin signaling. The mitochondria-associated glycerol-3-phosphate acyltransferase 1 (GPAT1) catalyzes the first committed step in glycerolipid synthesis, and its activity diverts fatty acids from mitochondrial β-oxidation. GPAT1 overexpression in mouse liver leads to hepatic steatosis even in the absence of overnutrition. The mice develop insulin resistance owing to the generation of saturated diacylglycerol and phosphatidic acid molecular species that reduce insulin signaling by activating PKCϵ and by suppressing mTORC2, respectively. Them2, a mitochondria-associated acyl-CoA thioesterase, also participates in the trafficking of fatty acids into oxidative
Identifiants
pubmed: 30523156
pii: S0021-9258(20)36846-0
doi: 10.1074/jbc.RA118.005184
pmc: PMC6369296
doi:
Substances chimiques
Fatty Acids
0
Glycerides
0
Glycerol-3-Phosphate O-Acyltransferase
EC 2.3.1.15
Protein Kinase C-epsilon
EC 2.7.11.13
ACOT13 protein, human
EC 3.1.2.-
Thiolester Hydrolases
EC 3.1.2.-
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
2009-2020Subventions
Organisme : American Heart Association-American Stroke Association
ID : 18POST33990445
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK056598
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK056626
Pays : United States
Organisme : NIDDK NIH HHS
ID : R37 DK048873
Pays : United States
Informations de copyright
© 2019 Tillander et al.
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