PPARγ Deacetylation Confers the Antiatherogenic Effect and Improves Endothelial Function in Diabetes Treatment.
Animals
Atherosclerosis
/ genetics
Blotting, Western
Chromatography, Liquid
Diabetes Mellitus
/ genetics
Interleukin-6
/ genetics
Male
Mice
Mice, Knockout
Mutation
/ genetics
NADPH Oxidase 2
/ genetics
Nitric Oxide Synthase Type II
/ genetics
PPAR gamma
/ genetics
Real-Time Polymerase Chain Reaction
Receptors, LDL
/ genetics
Thiazolidinediones
/ therapeutic use
Journal
Diabetes
ISSN: 1939-327X
Titre abrégé: Diabetes
Pays: United States
ID NLM: 0372763
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
03
03
2020
accepted:
11
05
2020
pubmed:
16
5
2020
medline:
19
12
2020
entrez:
16
5
2020
Statut:
ppublish
Résumé
Cardiovascular disease (CVD) is the leading cause of death in patients with diabetes, and tight glycemic control fails to reduce the risk of developing CVD. Thiazolidinediones (TZDs), a class of peroxisome proliferator-activated receptor γ (PPARγ) agonists, are potent insulin sensitizers with antiatherogenic properties, but their clinical use is limited by side effects. PPARγ deacetylation on two lysine residues (K268 and K293) induces brown remodeling of white adipose tissue and uncouples the adverse effects of TZDs from insulin sensitization. Here we show that PPARγ deacetylation confers antiatherogenic properties and retains the insulin-sensitizing effects of TZD while circumventing its detriments. We generated mice homozygous with mice with deacetylation-mimetic PPARγ mutations K268R/K293R (2KR) on an LDL-receptor knockout (
Identifiants
pubmed: 32409492
pii: db20-0217
doi: 10.2337/db20-0217
pmc: PMC7372079
doi:
Substances chimiques
Interleukin-6
0
PPAR gamma
0
Receptors, LDL
0
Thiazolidinediones
0
Nitric Oxide Synthase Type II
EC 1.14.13.39
NADPH Oxidase 2
EC 1.6.3.-
Banques de données
figshare
['10.2337/figshare.12280772']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1793-1803Subventions
Organisme : NHLBI NIH HHS
ID : R35 HL145228
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK112943
Pays : United States
Organisme : NIDDK NIH HHS
ID : R00 DK097455
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK064819
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL087123
Pays : United States
Informations de copyright
© 2020 by the American Diabetes Association.
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