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Urolithin A ameliorates obesity-induced metabolic cardiomyopathy in mice via mitophagy activation.
Huang, Jian-Rong; Zhang, Ming-Hua; Chen, Ying-Jie; Sun, Yu-Ling; Gao, Zhi-Min; Li, Zhuo-Jia; Zhang, Gui-Ping; Qin, Yuan; Dai, Xiao-Yan; Yu, Xi-Yong; Wu, Xiao-Qian.
Afiliación
  • Huang JR; The Fifth Affiliated Hospital & Key Laboratory of Molecular Target & Clinical Pharmacology and the State & NMPA KeyLaboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
  • Zhang MH; Cardiovascular Department, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510180, China.
  • Chen YJ; The Fifth Affiliated Hospital & Key Laboratory of Molecular Target & Clinical Pharmacology and the State & NMPA KeyLaboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
  • Sun YL; The Fifth Affiliated Hospital & Key Laboratory of Molecular Target & Clinical Pharmacology and the State & NMPA KeyLaboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
  • Gao ZM; The Fifth Affiliated Hospital & Key Laboratory of Molecular Target & Clinical Pharmacology and the State & NMPA KeyLaboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
  • Li ZJ; The Fifth Affiliated Hospital & Key Laboratory of Molecular Target & Clinical Pharmacology and the State & NMPA KeyLaboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
  • Zhang GP; The Fifth Affiliated Hospital & Key Laboratory of Molecular Target & Clinical Pharmacology and the State & NMPA KeyLaboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
  • Qin Y; The Fifth Affiliated Hospital & Key Laboratory of Molecular Target & Clinical Pharmacology and the State & NMPA KeyLaboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
  • Dai XY; The Fifth Affiliated Hospital & Key Laboratory of Molecular Target & Clinical Pharmacology and the State & NMPA KeyLaboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
  • Yu XY; The Fifth Affiliated Hospital & Key Laboratory of Molecular Target & Clinical Pharmacology and the State & NMPA KeyLaboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China. yuxycn@gzhmu.edu.cn.
  • Wu XQ; The Fifth Affiliated Hospital & Key Laboratory of Molecular Target & Clinical Pharmacology and the State & NMPA KeyLaboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China. wuxiaoqian@gzhmu.edu.cn.
Acta Pharmacol Sin ; 44(2): 321-331, 2023 Feb.
Article en En | MEDLINE | ID: mdl-35655094
Metabolic cardiomyopathy (MC) is characterized by intracellular lipid accumulation and utilizing fatty acids as a foremost energy source, thereby leading to excess oxidative stress and mitochondrial dysfunction. There is no effective therapy available yet. In this study we investigated whether defective mitophagy contributed to MC and whether urolithin A (UA), a naturally occurring microflora-derived metabolite, could protect against MC in experimental obese mice. Mice were fed high fat diet for 20 weeks to establish a diet-induced obese model. We showed that mitochondrial autophagy or mitophagy was significantly downregulated in the heart of experimental obese mice. UA (50 mg·kg-1·d-1, for 4 weeks) markedly activated mitophagy and ameliorated MC in obese mice by gavage. In PA-challenged H9C2 cardiomyocytes, UA (5 µM) significantly increased autophagosomes and decreased autolysosomes. Furthermore, UA administration rescued PINK1/Parkin-dependent mitophagy and relieved mitochondrial defects in the heart of obese mice, which led to improving cardiac diastolic function and ameliorating cardiac remodelling. In PA-challenged primarily isolated cardiomyocytes, both application of mitophagy inhibitor Mdivi-1 (15 µM) and silencing of mitophagy gene Parkin blunted the myocardial protective effect of UA. In summary, our data suggest that restoration of mitophagy with UA ameliorates symptoms of MC, which highlights a therapeutic potential of UA in the treatment of MC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Mitofagia / Cardiomiopatías Límite: Animals Idioma: En Revista: Acta Pharmacol Sin Asunto de la revista: FARMACOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Mitofagia / Cardiomiopatías Límite: Animals Idioma: En Revista: Acta Pharmacol Sin Asunto de la revista: FARMACOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos