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SIRT6 regulates obesity-induced oxidative stress via ENDOG/SOD2 signaling in the heart.
- Source :
-
Cell biology and toxicology [Cell Biol Toxicol] 2023 Aug; Vol. 39 (4), pp. 1489-1507. Date of Electronic Publication: 2022 Jul 07. - Publication Year :
- 2023
-
Abstract
- 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.<br /> (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)
Details
- Language :
- English
- ISSN :
- 1573-6822
- Volume :
- 39
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cell biology and toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 35798905
- Full Text :
- https://doi.org/10.1007/s10565-022-09735-z