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- Title
Omentin1 ameliorates myocardial ischemia-induced heart failure via SIRT3/FOXO3a-dependent mitochondrial dynamical homeostasis and mitophagy.
- Authors
Hu, Jingui; Liu, Tao; Fu, Fei; Cui, Zekun; Lai, Qiong; Zhang, Yuanyuan; Yu, Boyang; Liu, Fuming; Kou, Junping; Li, Fang
- Abstract
<bold>Background: </bold>Adipose tissue-derived adipokines are involved in various crosstalk between adipose tissue and other organs. Omentin1, a novel adipokine, exerts vital roles in the maintenance of body metabolism, insulin resistance and the like. However, the protective effect of omentin1 in myocardial ischemia (MI)-induced heart failure (HF) and its specific mechanism remains unclear and to be elucidated.<bold>Methods: </bold>The model of MI-induced HF mice and oxygen glucose deprivation (OGD)-injured cardiomyocytes were performed. Mice with overexpression of omentin1 were constructed by a fat-specific adeno-associated virus (AAV) vector system.<bold>Results: </bold>We demonstrated that circulating omentin1 level diminished in HF patients compared with healthy subjects. Furthermore, the fat-specific overexpression of omentin1 ameliorated cardiac function, cardiac hypertrophy, infarct size and cardiac pathological features, and also enhanced SIRT3/FOXO3a signaling in HF mice. Additionally, administration with AAV-omentin1 increased mitochondrial fusion and decreased mitochondrial fission in HF mice, as evidenced by up-regulated expression of Mfn2 and OPA1, and downregulation of p-Drp1(Ser616). Then, it also promoted PINK1/Parkin-dependent mitophagy. Simultaneously, treatment with recombinant omentin1 strengthened OGD-injured cardiomyocyte viability, restrained LDH release, and enhanced the mitochondrial accumulation of SIRT3 and nucleus transduction of FOXO3a. Besides, omentin1 also ameliorated unbalanced mitochondrial fusion-fission dynamics and activated mitophagy, thereby, improving the damaged mitochondria morphology and controlling mitochondrial quality in OGD-injured cardiomyocytes. Interestingly, SIRT3 played an important role in the improvement effects of omentin1 on mitochondrial function, unbalanced mitochondrial fusion-fission dynamics and mitophagy.<bold>Conclusion: </bold>Omentin1 improves MI-induced HF and myocardial injury by maintaining mitochondrial dynamical homeostasis and activating mitophagy via upregulation of SIRT3/FOXO3a signaling. This study provides evidence for further application of omentin1 in cardiovascular diseases from the perspective of crosstalk between heart and adipose tissue.
- Subjects
ENZYME metabolism; PROTEIN kinases; HOMEOSTASIS; FERRANS &; Powers Quality of Life Index; OXYGEN; MYOCARDIAL ischemia; MITOCHONDRIA; TRANSFERASES; RESEARCH funding; PEPTIDE hormones; GLUCOSE; HEART failure; MICE; ANIMALS; DISEASE complications
- Publication
Journal of Translational Medicine, 2022, Vol 20, Issue 1, p1
- ISSN
1479-5876
- Publication type
journal article
- DOI
10.1186/s12967-022-03642-x