Palmitate Induces Mitochondrial Energy Metabolism Disorder and Cellular Damage via the PPAR Signaling Pathway in Diabetic Cardiomyopathy
Xianyu Zhang, Min Mao, Zhong Zuo Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaCorrespondence: Zhong Zuo, Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No. 1, Medical Co...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2022-08-01
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| Series: | Diabetes, Metabolic Syndrome and Obesity |
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| Online Access: | https://www.dovepress.com/palmitate-induces-mitochondrial-energy-metabolism-disorder-and-cellula-peer-reviewed-fulltext-article-DMSO |
| _version_ | 1797758336627638272 |
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| author | Zhang X Mao M Zuo Z |
| author_facet | Zhang X Mao M Zuo Z |
| author_sort | Zhang X |
| collection | DOAJ |
| description | Xianyu Zhang, Min Mao, Zhong Zuo Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaCorrespondence: Zhong Zuo, Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No. 1, Medical College Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Email zuozhong@hospital.cqmu.edu.cnPurpose: To establish an in vitro lipotoxicity model with mouse cardiomyocytes (MCMs) and investigate the molecular mechanism of the peroxisome proliferator-activated receptors (PPAR) signaling on mitochondrial energy metabolism disorder and cellular injury in diabetic cardiomyopathy (DCM).Methods: Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on the differentially expressed genes (DEGs) of DCM. CCK-8 method was used to detect the proliferation inhibition effect of palmitate (PA) on MCMs. Oil red O staining and mRNA levels of CD36 were used to verify intracellular lipid accumulation. DCFH-DA method was used to determine the content of intracellular reactive oxygen species (ROS), and ATP levels were detected by the ATP Detection Kit. Transmission electron microscope (TEM) was used to observe the mitochondrial structure. Western blot was used to detect the expression levels of PPARα, PPARγ, P-mTOR, mTOR, PGC-1α, UCP2, and BNP. In addition, the expression of PPARγ was also detected by cellular immunofluorescence staining. BNP levels were detected by qRT-PCR and the ELISA Kit.Results: KEGG pathway analysis combined with GO analysis has shown that PPAR signaling played a significant regulatory role in mitochondrial biogenesis and fatty acid metabolism in DCM. Then, MCMs stimulated with PA for 24 h were selected as an in vitro lipotoxicity model. PA decreased cell viability, cell membrane shrinkage, and lipid accumulation. Meanwhile, PA-induced increase in cellular ROS led to ATP generation reduction and mitochondrial damage. Furthermore, the expression levels of p-mTOR- PPARα/γ were decreased, and the expressions of PGC-1α and UCP2 were increased. The levels of BNP were elevated, demonstrating PA impaired cardiomyocytes.Conclusion: Mitochondrial energy metabolism obstacle and cell injury appeared in cardiac lipotoxicity of DCM, associated with lipid accumulation and increased ROS, indicating a crosstalk with the PPAR pathway mediated mechanism.Keywords: diabetic cardiomyopathy, lipotoxicity, mitochondrial energy metabolism, cell damage, PPAR |
| first_indexed | 2024-03-12T18:28:32Z |
| format | Article |
| id | doaj.art-eabe37d5a3f6462684fe499a437d5b7d |
| institution | Directory Open Access Journal |
| issn | 1178-7007 |
| language | English |
| last_indexed | 2024-03-12T18:28:32Z |
| publishDate | 2022-08-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Diabetes, Metabolic Syndrome and Obesity |
| spelling | doaj.art-eabe37d5a3f6462684fe499a437d5b7d2023-08-02T08:26:41ZengDove Medical PressDiabetes, Metabolic Syndrome and Obesity1178-70072022-08-01Volume 152287229976969Palmitate Induces Mitochondrial Energy Metabolism Disorder and Cellular Damage via the PPAR Signaling Pathway in Diabetic CardiomyopathyZhang XMao MZuo ZXianyu Zhang, Min Mao, Zhong Zuo Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaCorrespondence: Zhong Zuo, Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No. 1, Medical College Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Email zuozhong@hospital.cqmu.edu.cnPurpose: To establish an in vitro lipotoxicity model with mouse cardiomyocytes (MCMs) and investigate the molecular mechanism of the peroxisome proliferator-activated receptors (PPAR) signaling on mitochondrial energy metabolism disorder and cellular injury in diabetic cardiomyopathy (DCM).Methods: Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on the differentially expressed genes (DEGs) of DCM. CCK-8 method was used to detect the proliferation inhibition effect of palmitate (PA) on MCMs. Oil red O staining and mRNA levels of CD36 were used to verify intracellular lipid accumulation. DCFH-DA method was used to determine the content of intracellular reactive oxygen species (ROS), and ATP levels were detected by the ATP Detection Kit. Transmission electron microscope (TEM) was used to observe the mitochondrial structure. Western blot was used to detect the expression levels of PPARα, PPARγ, P-mTOR, mTOR, PGC-1α, UCP2, and BNP. In addition, the expression of PPARγ was also detected by cellular immunofluorescence staining. BNP levels were detected by qRT-PCR and the ELISA Kit.Results: KEGG pathway analysis combined with GO analysis has shown that PPAR signaling played a significant regulatory role in mitochondrial biogenesis and fatty acid metabolism in DCM. Then, MCMs stimulated with PA for 24 h were selected as an in vitro lipotoxicity model. PA decreased cell viability, cell membrane shrinkage, and lipid accumulation. Meanwhile, PA-induced increase in cellular ROS led to ATP generation reduction and mitochondrial damage. Furthermore, the expression levels of p-mTOR- PPARα/γ were decreased, and the expressions of PGC-1α and UCP2 were increased. The levels of BNP were elevated, demonstrating PA impaired cardiomyocytes.Conclusion: Mitochondrial energy metabolism obstacle and cell injury appeared in cardiac lipotoxicity of DCM, associated with lipid accumulation and increased ROS, indicating a crosstalk with the PPAR pathway mediated mechanism.Keywords: diabetic cardiomyopathy, lipotoxicity, mitochondrial energy metabolism, cell damage, PPARhttps://www.dovepress.com/palmitate-induces-mitochondrial-energy-metabolism-disorder-and-cellula-peer-reviewed-fulltext-article-DMSOdiabetic cardiomyopathylipotoxicitymitochondrial energy metabolismcell |
| spellingShingle | Zhang X Mao M Zuo Z Palmitate Induces Mitochondrial Energy Metabolism Disorder and Cellular Damage via the PPAR Signaling Pathway in Diabetic Cardiomyopathy Diabetes, Metabolic Syndrome and Obesity diabetic cardiomyopathy lipotoxicity mitochondrial energy metabolism cell |
| title | Palmitate Induces Mitochondrial Energy Metabolism Disorder and Cellular Damage via the PPAR Signaling Pathway in Diabetic Cardiomyopathy |
| title_full | Palmitate Induces Mitochondrial Energy Metabolism Disorder and Cellular Damage via the PPAR Signaling Pathway in Diabetic Cardiomyopathy |
| title_fullStr | Palmitate Induces Mitochondrial Energy Metabolism Disorder and Cellular Damage via the PPAR Signaling Pathway in Diabetic Cardiomyopathy |
| title_full_unstemmed | Palmitate Induces Mitochondrial Energy Metabolism Disorder and Cellular Damage via the PPAR Signaling Pathway in Diabetic Cardiomyopathy |
| title_short | Palmitate Induces Mitochondrial Energy Metabolism Disorder and Cellular Damage via the PPAR Signaling Pathway in Diabetic Cardiomyopathy |
| title_sort | palmitate induces mitochondrial energy metabolism disorder and cellular damage via the ppar signaling pathway in diabetic cardiomyopathy |
| topic | diabetic cardiomyopathy lipotoxicity mitochondrial energy metabolism cell |
| url | https://www.dovepress.com/palmitate-induces-mitochondrial-energy-metabolism-disorder-and-cellula-peer-reviewed-fulltext-article-DMSO |
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