PEDF Overexpression Ameliorates Cardiac Lipotoxicity in Diabetic Cardiomyopathy via Regulation of Energy Metabolism
Tuohua Mao, Ye Wang Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of ChinaCorrespondence: Ye Wang, Department of Endocrinology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang, Wuhan, Hubei, 430060, People’s Republic of China, Email...
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2025-01-01
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| description | Tuohua Mao, Ye Wang Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of ChinaCorrespondence: Ye Wang, Department of Endocrinology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang, Wuhan, Hubei, 430060, People’s Republic of China, Email wye2018@whu.edu.cnBackground: Early alterations in cardiac energy metabolism and lipotoxicity are crucial factors in the pathogenesis and progression of diabetic cardiomyopathy (DCM). The excessive accumulation of lipid metabolic intermediates within the myocardium can lead to increased production of reactive oxygen species (ROS) and promote apoptosis. Pigment epithelium-derived factor (PEDF) has been shown to regulate cardiac energy metabolism; however, its role in modulating energy metabolism, ROS generation, and apoptosis in the context of DCM requires further investigation.Methods: PEDF was overexpressed in db/db mice via tail vein injection of adeno-associated virus 9(AAV9)-PEDF. At week 24, assessments were conducted on cardiac hypertrophy, fibrosis, cardiac function, and alterations in energy metabolism. Additionally, H9c2 cells were transfected with a PEDF plasmid and cultured under HG+PA conditions (33 mm glucose + 250 μM palmitic acid) for 24 hours. Subsequent analyses focused on changes in energy metabolism, ROS levels, and apoptosis.Results: At 24 weeks, db/db mice exhibited hallmark features of DCM, including hyperglycemia, hyperlipidemia, cardiac hypertrophy, fibrosis, and diastolic dysfunction. Overexpression of PEDF reversed cardiac remodeling in these mice. In both db/db mice and HG+PA-treated H9c2 cells, PEDF overexpression modulated cardiac energy metabolism, mitigated lipotoxicity, and promoted the expression of adipose triglyceride lipase(ATGL) and glucose transporter type 4(Glut4) while inhibiting the expression of peroxisome proliferator-activated receptor alpha (PPARα), carnitine palmitoyltransferase 1 alpha (CPT1α), and scavenger receptor B2 (CD36). Additionally, PEDF overexpression reduced ROS generation and apoptosis in db/db mice myocardium and HG+PA-treated h9c2 cells.Conclusion: PEDF can effectively prevent cardiac hypertrophy, fibrosis remodeling, and the deterioration of diastolic dysfunction in DCM by modulating cardiac energy metabolism and mitigating ROS production and apoptosis induced by lipotoxicity.Keywords: PEDF, diabetic cardiomyopathy, metabolic disorders, lipotoxicity, reactive oxygen species, apoptosis |
| format | Article |
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| series | Diabetes, Metabolic Syndrome and Obesity |
| spelling | doaj-art-b9f8872f809e4ac58d964926c4cf3d8e2025-01-27T18:05:34ZengDove Medical PressDiabetes, Metabolic Syndrome and Obesity1178-70072025-01-01Volume 1821723199649PEDF Overexpression Ameliorates Cardiac Lipotoxicity in Diabetic Cardiomyopathy via Regulation of Energy MetabolismMao TWang YTuohua Mao, Ye Wang Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of ChinaCorrespondence: Ye Wang, Department of Endocrinology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang, Wuhan, Hubei, 430060, People’s Republic of China, Email wye2018@whu.edu.cnBackground: Early alterations in cardiac energy metabolism and lipotoxicity are crucial factors in the pathogenesis and progression of diabetic cardiomyopathy (DCM). The excessive accumulation of lipid metabolic intermediates within the myocardium can lead to increased production of reactive oxygen species (ROS) and promote apoptosis. Pigment epithelium-derived factor (PEDF) has been shown to regulate cardiac energy metabolism; however, its role in modulating energy metabolism, ROS generation, and apoptosis in the context of DCM requires further investigation.Methods: PEDF was overexpressed in db/db mice via tail vein injection of adeno-associated virus 9(AAV9)-PEDF. At week 24, assessments were conducted on cardiac hypertrophy, fibrosis, cardiac function, and alterations in energy metabolism. Additionally, H9c2 cells were transfected with a PEDF plasmid and cultured under HG+PA conditions (33 mm glucose + 250 μM palmitic acid) for 24 hours. Subsequent analyses focused on changes in energy metabolism, ROS levels, and apoptosis.Results: At 24 weeks, db/db mice exhibited hallmark features of DCM, including hyperglycemia, hyperlipidemia, cardiac hypertrophy, fibrosis, and diastolic dysfunction. Overexpression of PEDF reversed cardiac remodeling in these mice. In both db/db mice and HG+PA-treated H9c2 cells, PEDF overexpression modulated cardiac energy metabolism, mitigated lipotoxicity, and promoted the expression of adipose triglyceride lipase(ATGL) and glucose transporter type 4(Glut4) while inhibiting the expression of peroxisome proliferator-activated receptor alpha (PPARα), carnitine palmitoyltransferase 1 alpha (CPT1α), and scavenger receptor B2 (CD36). Additionally, PEDF overexpression reduced ROS generation and apoptosis in db/db mice myocardium and HG+PA-treated h9c2 cells.Conclusion: PEDF can effectively prevent cardiac hypertrophy, fibrosis remodeling, and the deterioration of diastolic dysfunction in DCM by modulating cardiac energy metabolism and mitigating ROS production and apoptosis induced by lipotoxicity.Keywords: PEDF, diabetic cardiomyopathy, metabolic disorders, lipotoxicity, reactive oxygen species, apoptosishttps://www.dovepress.com/pedf-overexpression-ameliorates-cardiac-lipotoxicity-in-diabetic-cardi-peer-reviewed-fulltext-article-DMSOpedfdiabetic cardiomyopathymetabolic disorderslipotoxicityreactive oxygen speciesapoptosis |
| spellingShingle | Mao T Wang Y PEDF Overexpression Ameliorates Cardiac Lipotoxicity in Diabetic Cardiomyopathy via Regulation of Energy Metabolism Diabetes, Metabolic Syndrome and Obesity pedf diabetic cardiomyopathy metabolic disorders lipotoxicity reactive oxygen species apoptosis |
| title | PEDF Overexpression Ameliorates Cardiac Lipotoxicity in Diabetic Cardiomyopathy via Regulation of Energy Metabolism |
| title_full | PEDF Overexpression Ameliorates Cardiac Lipotoxicity in Diabetic Cardiomyopathy via Regulation of Energy Metabolism |
| title_fullStr | PEDF Overexpression Ameliorates Cardiac Lipotoxicity in Diabetic Cardiomyopathy via Regulation of Energy Metabolism |
| title_full_unstemmed | PEDF Overexpression Ameliorates Cardiac Lipotoxicity in Diabetic Cardiomyopathy via Regulation of Energy Metabolism |
| title_short | PEDF Overexpression Ameliorates Cardiac Lipotoxicity in Diabetic Cardiomyopathy via Regulation of Energy Metabolism |
| title_sort | pedf overexpression ameliorates cardiac lipotoxicity in diabetic cardiomyopathy via regulation of energy metabolism |
| topic | pedf diabetic cardiomyopathy metabolic disorders lipotoxicity reactive oxygen species apoptosis |
| url | https://www.dovepress.com/pedf-overexpression-ameliorates-cardiac-lipotoxicity-in-diabetic-cardi-peer-reviewed-fulltext-article-DMSO |
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