Enhancing fatty acid utilization ameliorates mitochondrial fragmentation and cardiac dysfunction via rebalancing optic atrophy 1 processing in the failing heart

Guo, Yongzheng; Wang, Zhen; Qin, Xinghua; Xu, Jie; Hou, Zuoxu; Yang, Hongyan; Mao, Xuechao; Xing, Wenjuan; Li, Xiaoliang; Xing, Zhen; Gao, Feng

doi:10.1093/cvr/cvy052

Cited by 52 publications

(32 citation statements)

References 49 publications

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“…Another study found that the KD reduces midlife mortality and improves memory in aging mice [19]. Our previous work demonstrated that feeding a high-fat diet (45% of calories derived from fatty acids) feeding for 2 months after transverse aortic constriction (TAC) surgery enhanced fatty acid utilization and prevented the development of heart failure in mice [20]. These findings suggested that the KD, a high-fat and low-carbohydrate diet, may exert health-promoting effects in both humans and animals.…”

Section: Discussionmentioning

confidence: 99%

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Ketogenic Diet Ameliorates Cardiac Dysfunction via Balancing Mitochondrial Dynamics and Inhibiting Apoptosis in Type 2 Diabetic Mice

Guo¹,

Zhang²,

Shang³

et al. 2020

Aging and disease

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The ketogenic diet (KD) has been widely used in clinical studies and shown to hace an anti-diabetic effect, but the underlying mechanisms have not been fully elaborated. Our aim was to investigate the effects and the underling mechanisms of the KD on cardiac function in db/db mice. In the present study, db/db mice were subjected to a normal diet (ND) or KD. Fasting blood glucose, cardiac function and morphology, mitochondrial dynamics, oxidative stress, and apoptosis were measured 8 weeks post KD treatment. Compared with the ND, the KD improved glycemic control and protected against diabetic cardiomyopathy in db/db mice, and improved mitochondrial function, as well as reduced oxidative stress were observed in hearts. In addition, KD treatment exerted an anti-apoptotic effect in the heart of db/db mice. Further data showed that the PI3K/Akt pathway was involved in this protective effect. Our data demonstrated that KD treatment ameliorates cardiac dysfunction by inhibiting apoptosis via activating the PI3K-Akt pathway in type 2 diabetic mice, suggesting that the KD is a promising lifestyle intervention to protect against diabetic cardiomyopathy.

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Section: Discussionmentioning

confidence: 99%

“…Histological studies were performed as described previously [20]. Briefly, cardiac tissues were paraffin embedded and sectioned at a thickness of 5 μm for hematoxylin and eosin staining.…”

Section: Assessment Of Cardiac Structure and Functionmentioning

confidence: 99%

Ketogenic Diet Ameliorates Cardiac Dysfunction via Balancing Mitochondrial Dynamics and Inhibiting Apoptosis in Type 2 Diabetic Mice

Guo¹,

Zhang²,

Shang³

et al. 2020

Aging and disease

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“…Alterations in mitochondrial dynamics, respiratory capacity, and ATP synthesis play an important role in the chronic cardiac energy deficit observed in heart failure [ 91 ]. Improved fatty acid utilization via dietary modification significantly ameliorates mitochondrial fragmentation and cardiac dysfunction [ 92 ].…”

Section: The Obesity Paradoxmentioning

confidence: 99%

The Impact of Obesity on the Cardiovascular System

Csige

Ujvárosy

Szabó

et al. 2018

Journal of Diabetes Research

334

227

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Obesity is a growing health problem worldwide. It is associated with an increased cardiovascular risk on the one hand of obesity itself and on the other hand of associated medical conditions (hypertension, diabetes, insulin resistance, and sleep apnoea syndrome). Obesity has an important role in atherosclerosis and coronary artery disease. Obesity leads to structural and functional changes of the heart, which causes heart failure. The altered myocardial structure increases the risk of atrial fibrillation and sudden cardiac death. However, obesity also has a protective effect on the clinical outcome of underlying cardiovascular disease, the phenomenon called obesity paradox. The improved cardiac imaging techniques allow the early detection of altered structure and function of the heart in obese patients. In this review, we attempt to summarize the relationship between obesity and cardiovascular diseases and outline the underlying mechanisms. The demonstrated new techniques of cardiac diagnostic procedures allow for the early detection and treatment of subclinical medical conditions and, therefore, the prevention of cardiovascular events.

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“…Furthermore, decreased OPA1 is associated with the progression of autoimmune myocarditis via the repression of mitochondrial fusion . In the failing heart, the overexpression of OPA1 reverses mitochondrial function and improves cardiac performance . Mechanistically, OPA1 expression is potentially regulated by the AMPK pathway, which is also reported to be associated with mitophagy modification.…”

Section: Introductionmentioning

confidence: 99%

“…7 In the failing heart, the overexpression of OPA1 reverses mitochondrial function and improves cardiac performance. 31 Mechanistically, OPA1 expression is potentially regulated by the AMPK pathway, 5 which is also reported to be associated with mitophagy modification. Along with the well-documented role played by OPA1-related mitochondrial fusion and mitophagy in cardioprotection, it is very worthwhile to explore whether melatonin protects the reperfused heart by activating OPA1-related mitochondrial fusion and mitophagy in a manner dependent on the AMPK signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

Melatonin attenuates myocardial ischemia‐reperfusion injury via improving mitochondrial fusion/mitophagy and activating the AMPK‐OPA1 signaling pathways

Zhang

Wang

et al. 2019

Journal of Pineal Research

270

173

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Optic atrophy 1 (OPA1)‐related mitochondrial fusion and mitophagy are vital to sustain mitochondrial homeostasis under stress conditions. However, no study has confirmed whether OPA1‐related mitochondrial fusion/mitophagy is activated by melatonin and, consequently, attenuates cardiomyocyte death and mitochondrial stress in the setting of cardiac ischemia‐reperfusion (I/R) injury. Our results indicated that OPA1, mitochondrial fusion, and mitophagy were significantly repressed by I/R injury, accompanied by infarction area expansion, heart dysfunction, myocardial inflammation, and cardiomyocyte oxidative stress. However, melatonin treatment maintained myocardial function and cardiomyocyte viability, and these effects were highly dependent on OPA1‐related mitochondrial fusion/mitophagy. At the molecular level, OPA1‐related mitochondrial fusion/mitophagy, which was normalized by melatonin, substantially rectified the excessive mitochondrial fission, promoted mitochondria energy metabolism, sustained mitochondrial function, and blocked cardiomyocyte caspase‐9‐involved mitochondrial apoptosis. However, genetic approaches with a cardiac‐specific knockout of OPA1 abolished the beneficial effects of melatonin on cardiomyocyte survival and mitochondrial homeostasis in vivo and in vitro. Furthermore, we demonstrated that melatonin affected OPA1 stabilization via the AMPK signaling pathway and that blockade of AMPK repressed OPA1 expression and compromised the cardioprotective action of melatonin. Overall, our results confirm that OPA1‐related mitochondrial fusion/mitophagy is actually modulated by melatonin in the setting of cardiac I/R injury. Moreover, manipulation of the AMPK‐OPA1‐mitochondrial fusion/mitophagy axis via melatonin may be a novel therapeutic approach to reduce cardiac I/R injury.

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Enhancing fatty acid utilization ameliorates mitochondrial fragmentation and cardiac dysfunction via rebalancing optic atrophy 1 processing in the failing heart

Abstract: These findings demonstrate that enhancing FA utilization ameliorates mitochondrial fragmentation and cardiac dysfunction via rebalancing OPA1 processing in pressure overload-induced HF, suggesting a unique metabolic intervention approach to improving cardiac functions in HF.

Cited by 52 publications

References 49 publications

Ketogenic Diet Ameliorates Cardiac Dysfunction via Balancing Mitochondrial Dynamics and Inhibiting Apoptosis in Type 2 Diabetic Mice

Ketogenic Diet Ameliorates Cardiac Dysfunction via Balancing Mitochondrial Dynamics and Inhibiting Apoptosis in Type 2 Diabetic Mice

The Impact of Obesity on the Cardiovascular System

Melatonin attenuates myocardial ischemia‐reperfusion injury via improving mitochondrial fusion/mitophagy and activating the AMPK‐OPA1 signaling pathways

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