Oral Sulforaphane Intervention Protects Against Diabetic Cardiomyopathy in db/db Mice: Focus on Cardiac Lipotoxicity and Substrate Metabolism
The protective effect of cruciferae-derived sulforaphane (SFN) on diabetic cardiomyopathy (DCM) has garnered increasing attention. However, no studies have specifically explored its mechanistic involvement in cardiac substrate metabolism and mitochondrial function. To address this gap, Type 2 diabet...
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MDPI AG
2025-05-01
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| Series: | Antioxidants |
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| author | Pan Wang Ziling Wang Xinyuan Jin Mengdi Zhang Mengfan Shen Dan Li |
| author_facet | Pan Wang Ziling Wang Xinyuan Jin Mengdi Zhang Mengfan Shen Dan Li |
| author_sort | Pan Wang |
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| description | The protective effect of cruciferae-derived sulforaphane (SFN) on diabetic cardiomyopathy (DCM) has garnered increasing attention. However, no studies have specifically explored its mechanistic involvement in cardiac substrate metabolism and mitochondrial function. To address this gap, Type 2 diabetes mellitus (T2DM) db/db mice were orally gavaged with vehicle or 10 mg/kg body weight SFN every other day for 16 weeks, with vehicle-treated wild-type mice as controls. SFN intervention (SFN-I) alleviated hyperglycemia, dyslipidemia, HOMA-IR, serum MDA levels, and liver inflammation. Furthermore, SFN-I improved the lipotoxicity-related phenotype of T2DM cardiomyopathy, manifested as attenuation of diastolic dysfunction, cardiac injury, fibrosis, lipid accumulation and peroxidation, ROS generation, and decreased mitochondrial complex I and II activities and ATP content, despite having no effect on ceramide abnormalities. Protein expression data revealed that the model mice exhibited upregulated cardiac CD36, H-FABP, FATP4, CPT1B, PPARα, and PDK4 but downregulated GLUT4, with unchanged MPC1 and MPC2. Notably, SFN-I significantly attenuated the increase in CD36, H-FABP, CPT1B, and PPARα. These results suggest that chronic oral SFN-I protects against DCM by mitigating overall metabolic dysregulation and inhibiting cardiolipotoxicity. The latter might involve controlling cardiac fatty acid metabolism and improving mitochondrial function, rather than promoting glucose metabolism. |
| format | Article |
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| language | English |
| publishDate | 2025-05-01 |
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| spelling | doaj-art-2bcbb6872eec42cf84ccbda657cf84582025-08-20T02:33:39ZengMDPI AGAntioxidants2076-39212025-05-0114560310.3390/antiox14050603Oral Sulforaphane Intervention Protects Against Diabetic Cardiomyopathy in db/db Mice: Focus on Cardiac Lipotoxicity and Substrate MetabolismPan Wang0Ziling Wang1Xinyuan Jin2Mengdi Zhang3Mengfan Shen4Dan Li5Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, ChinaDepartment of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, ChinaDepartment of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, ChinaDepartment of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, ChinaDepartment of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, ChinaDepartment of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, ChinaThe protective effect of cruciferae-derived sulforaphane (SFN) on diabetic cardiomyopathy (DCM) has garnered increasing attention. However, no studies have specifically explored its mechanistic involvement in cardiac substrate metabolism and mitochondrial function. To address this gap, Type 2 diabetes mellitus (T2DM) db/db mice were orally gavaged with vehicle or 10 mg/kg body weight SFN every other day for 16 weeks, with vehicle-treated wild-type mice as controls. SFN intervention (SFN-I) alleviated hyperglycemia, dyslipidemia, HOMA-IR, serum MDA levels, and liver inflammation. Furthermore, SFN-I improved the lipotoxicity-related phenotype of T2DM cardiomyopathy, manifested as attenuation of diastolic dysfunction, cardiac injury, fibrosis, lipid accumulation and peroxidation, ROS generation, and decreased mitochondrial complex I and II activities and ATP content, despite having no effect on ceramide abnormalities. Protein expression data revealed that the model mice exhibited upregulated cardiac CD36, H-FABP, FATP4, CPT1B, PPARα, and PDK4 but downregulated GLUT4, with unchanged MPC1 and MPC2. Notably, SFN-I significantly attenuated the increase in CD36, H-FABP, CPT1B, and PPARα. These results suggest that chronic oral SFN-I protects against DCM by mitigating overall metabolic dysregulation and inhibiting cardiolipotoxicity. The latter might involve controlling cardiac fatty acid metabolism and improving mitochondrial function, rather than promoting glucose metabolism.https://www.mdpi.com/2076-3921/14/5/603sulforaphanecruciferaediabetic cardiomyopathydiabetes mellituslipotoxicitysubstrate metabolism |
| spellingShingle | Pan Wang Ziling Wang Xinyuan Jin Mengdi Zhang Mengfan Shen Dan Li Oral Sulforaphane Intervention Protects Against Diabetic Cardiomyopathy in db/db Mice: Focus on Cardiac Lipotoxicity and Substrate Metabolism Antioxidants sulforaphane cruciferae diabetic cardiomyopathy diabetes mellitus lipotoxicity substrate metabolism |
| title | Oral Sulforaphane Intervention Protects Against Diabetic Cardiomyopathy in db/db Mice: Focus on Cardiac Lipotoxicity and Substrate Metabolism |
| title_full | Oral Sulforaphane Intervention Protects Against Diabetic Cardiomyopathy in db/db Mice: Focus on Cardiac Lipotoxicity and Substrate Metabolism |
| title_fullStr | Oral Sulforaphane Intervention Protects Against Diabetic Cardiomyopathy in db/db Mice: Focus on Cardiac Lipotoxicity and Substrate Metabolism |
| title_full_unstemmed | Oral Sulforaphane Intervention Protects Against Diabetic Cardiomyopathy in db/db Mice: Focus on Cardiac Lipotoxicity and Substrate Metabolism |
| title_short | Oral Sulforaphane Intervention Protects Against Diabetic Cardiomyopathy in db/db Mice: Focus on Cardiac Lipotoxicity and Substrate Metabolism |
| title_sort | oral sulforaphane intervention protects against diabetic cardiomyopathy in db db mice focus on cardiac lipotoxicity and substrate metabolism |
| topic | sulforaphane cruciferae diabetic cardiomyopathy diabetes mellitus lipotoxicity substrate metabolism |
| url | https://www.mdpi.com/2076-3921/14/5/603 |
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