Dataset Information

Exercise Training Promotes Cardiac Hydrogen Sulfide Biosynthesis and Mitigates Pyroptosis to Prevent High-Fat Diet-Induced Diabetic Cardiomyopathy.

ABSTRACT: Obesity increases the risk of developing diabetes and subsequently, diabetic cardiomyopathy (DMCM). Reduced cardioprotective antioxidant hydrogen sulfide (H2S) and increased inflammatory cell death via pyroptosis contribute to adverse cardiac remodeling and DMCM. Although exercise training (EX) has cardioprotective effects, it is unclear whether EX mitigates obesity-induced DMCM by increasing H?S biosynthesis and mitigating pyroptosis in the heart. C57BL6 mice were fed a high-fat diet (HFD) while undergoing treadmill EX for 20 weeks. HFD mice developed obesity, hyperglycemia, and insulin resistance, which were reduced by EX. Left ventricle pressure-volume measurement revealed that obese mice developed reduced diastolic function with preserved ejection fraction, which was improved by EX. Cardiac dysfunction was accompanied by increased cardiac pyroptosis signaling, structural remodeling, and metabolic remodeling, indicated by accumulation of lipid droplets in the heart. Notably, EX increased cardiac H?S concentration and expression of H?S biosynthesis enzymes. HFD-induced obesity led to features of type 2 diabetes (T2DM), and subsequently DMCM. EX during the HFD regimen prevented the development of DMCM, possibly by promoting H?S-mediated cardioprotection and alleviating pyroptosis. This is the first report of EX modulating H?S and pyroptotic signaling in the heart.

SUBMITTER: Kar S

PROVIDER: S-EPMC6943713 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Exercise Training Promotes Cardiac Hydrogen Sulfide Biosynthesis and Mitigates Pyroptosis to Prevent High-Fat Diet-Induced Diabetic Cardiomyopathy.

Kar Sumit S Shahshahan Hamid R HR Hackfort Bryan T BT Yadav Santosh K SK Yadav Roopali R Kambis Tyler N TN Lefer David J DJ Mishra Paras K PK

Antioxidants (Basel, Switzerland) 20191211 12

Obesity increases the risk of developing diabetes and subsequently, diabetic cardiomyopathy (DMCM). Reduced cardioprotective antioxidant hydrogen sulfide (H<sub>2</sub>S) and increased inflammatory cell death via pyroptosis contribute to adverse cardiac remodeling and DMCM. Although exercise training (EX) has cardioprotective effects, it is unclear whether EX mitigates obesity-induced DMCM by increasing H₂S biosynthesis and mitigating pyroptosis in the heart. C57BL6 mice were fed a high-fat diet ...[more]

PMID: 31835893

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Project description:Activation of the systemic and myocardial rennin-angiotensin-aldosterone system (RAAS) by hyperglycemia plays a critical role in the development of diabetic cardiomyopathy. To test the hypothesis that AngIV protects against diabetic cardiomyopathy via stimulation of AT4R and inhibition of overactive autophagy, diabetic mice were treated with low-, medium- and high-dose AngIV, AT4R antagonist divalinal, forkhead box protein O1 (FoxO1) inhibitor AS1842856 (AS) or their combinations. In vitro, cardiomyocytes were treated with different concentrations of glucose, low-, medium- and high-dose AngIV, divalinal, FoxO1-overexpression plasmid (FoxO1-OE), AS or their combinations. The results showed that AngIV treatment dose-dependently attenuated left ventricular dysfunction, remodeling, fibrosis, and myocyte apoptosis in diabetic mice. Besides, autophagy and FoxO1 protein expression enhanced by diabetes were dose-dependently suppressed by AngIV treatment. However, these cardioprotective effects of AngIV were completely abolished by divalinal administration. Bioinformatic analyses revealed that the differentially expressed genes were enriched in autophagy, apoptosis, and FoxO signaling pathways among control, diabetes, and diabetes+high-dose AngIV groups. Similar to AngIV, AS treatment ameliorated diabetic cardiomyopathy in mice. In vitro, AngIV inhibited collagen expression, apoptosis, overactive autophagy flux, and FoxO1 nuclear translocation induced by high glucose in cardiomyocytes. However, these protective effects of AngIV were completely blocked by the use of divalinal or FoxO1-OE, and these detrimental effects were reversed by the additional administration of AS. In summary, AngIV treatment dose-dependently attenuated left ventricular dysfunction and remodeling in a mouse model of diabetic cardiomyopathy, and the mechanism involved stimulation of AT4R, suppression of FoxO1 nuclear translocation and inhibition of FoxO1-mediated overactive autophagy.

Dataset Information

Exercise Training Promotes Cardiac Hydrogen Sulfide Biosynthesis and Mitigates Pyroptosis to Prevent High-Fat Diet-Induced Diabetic Cardiomyopathy.

Publications

Exercise Training Promotes Cardiac Hydrogen Sulfide Biosynthesis and Mitigates Pyroptosis to Prevent High-Fat Diet-Induced Diabetic Cardiomyopathy.

Similar Datasets

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