SIRT6 regulates obesity-induced oxidative stress via ENDOG/SOD2 signaling in the heart.
Endonuclease G
High-fat diet
Oxidative stress
Sirtuin 6
Superoxide dismutase 2
Journal
Cell biology and toxicology
ISSN: 1573-6822
Titre abrégé: Cell Biol Toxicol
Pays: Switzerland
ID NLM: 8506639
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
received:
06
04
2022
accepted:
07
06
2022
medline:
15
8
2023
pubmed:
8
7
2022
entrez:
7
7
2022
Statut:
ppublish
Résumé
The sirtuin 6 (SIRT6) participates in regulating glucose and lipid homeostasis. However, the function of SIRT6 in the process of cardiac pathogenesis caused by obesity-associated lipotoxicity remains to be unveiled. This study was designed to elucidate the role of SIRT6 in the pathogenesis of cardiac injury due to nutrition overload-induced obesity and explore the downstream signaling pathways affecting oxidative stress in the heart. In this study, we used Sirt6 cardiac-specific knockout murine models treated with a high-fat diet (HFD) feeding to explore the function and mechanism of SIRT6 in the heart tissue during HFD-induced obesity. We also took advantage of neonatal cardiomyocytes to study the role and downstream molecules of SIRT6 during HFD-induced injury in vitro, in which intracellular oxidative stress and mitochondrial content were assessed. We observed that during HFD-induced obesity, Sirt6 loss-of-function aggravated cardiac injury including left ventricular hypertrophy and lipid accumulation. Our results evidenced that upon increased fatty acid uptake, SIRT6 positively regulated the expression of endonuclease G (ENDOG), which is a mitochondrial-resident molecule that plays an important role in mitochondrial biogenesis and redox homeostasis. Our results also showed that SIRT6 positively regulated superoxide dismutase 2 (SOD2) expression post-transcriptionally via ENDOG. Our study gives a new sight into SIRT6 beneficial role in mitochondrial biogenesis of cardiomyocytes. Our data also show that SIRT6 is required to reduce intracellular oxidative stress in the heart triggered by high-fat diet-induced obesity, involving the control of ENDOG/SOD2.
Identifiants
pubmed: 35798905
doi: 10.1007/s10565-022-09735-z
pii: 10.1007/s10565-022-09735-z
doi:
Substances chimiques
superoxide dismutase 2
EC 1.15.1.1
endonuclease G
EC 3.1.21.-
Sirtuins
EC 3.5.1.-
Lipids
0
Sirt6 protein, mouse
EC 2.4.2.31
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1489-1507Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature B.V.
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