Key result
MitoTEMPO treatment prevented insulin resistance and diastolic dysfunction in high-fat diet-fed mice, which otherwise showed reduced diastolic circumferential strain rate.
Why the study?
Does MitoTEMPO prevent diastolic dysfunction and insulin resistance in a high-fat diet mouse model?
Does MitoTEMPO prevent diastolic dysfunction and insulin resistance in a high-fat diet mouse model?
MitoTEMPO treatment prevented insulin resistance and diastolic dysfunction in a high-fat diet mouse model, suggesting mitochondrial oxidative stress is involved in their pathophysiology.
Answers are grounded in this paper and cite their sources.
Implicates mitochondrial ROS in metabolic diastolic dysfunction; extends preclinical models but leaves human translation open.
BACKGROUND: Diabetes mellitus (DM) is associated with mitochondrial oxidative stress. We have shown that myocardial oxidative stress leads to diastolic dysfunction in a hypertensive mouse model. Therefore, we hypothesized that diabetes mellitus could cause diastolic dysfunction through mitochondrial oxidative stress and that a mitochondria-targeted antioxidant (MitoTEMPO) could prevent diastolic dysfunction in a diabetic mouse model. METHODS AND RESULTS: C57BL/6J mice were fed either 60 kcal % fat diet (high-fat diet [HFD]) or normal chow (control) for 8 weeks with or without concurrent MitoTEMPO administration, followed by in vivo assessment of diastolic function and ex vivo studies. HFD mice developed impaired glucose tolerance compared with the control (serum glucose=495±45 mg/dL versus 236±30 mg/dL at 60 minutes after intraperitoneal glucose injection, P<0.05). Myocardial tagged cardiac magnetic resonance imaging showed significantly reduced diastolic circumferential strain (Ecc) rate in the HFD mice compared with controls (5.0±0.3 1/s versus 7.4±0.5 1/s, P<0.05), indicating diastolic dysfunction in the HFD mice. Systolic function was comparable in both groups (left ventricular ejection fraction=66.4±1.4% versus 66.7±1.2%, P>0.05). MitoTEMPO-treated HFD mice showed significant reduction in mitochondria reactive oxygen species, S-glutathionylation of cardiac myosin binding protein C, and diastolic dysfunction, comparable to the control. The fasting insulin levels of MitoTEMPO-treated HFD mice were also comparable to the controls (P>0.05). CONCLUSIONS: MitoTEMPO treatment prevented insulin resistance and diastolic dysfunction, suggesting that mitochondrial oxidative stress may be involved in the pathophysiology of both conditions.
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Jeong et al. (2016) studied Diabetes mellitus, insulin resistance, and cardiac diastolic dysfunction. MitoTEMPO vs. High-fat diet without MitoTEMPO was evaluated on Diastolic circumferential strain (Ecc) rate and glucose tolerance. MitoTEMPO treatment prevented insulin resistance and diastolic dysfunction in high-fat diet-fed mice, which otherwise showed reduced diastolic circumferential strain rate.
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