Retinol dehydrogenase 10 reduction mediated retinol metabolism disorder promotes diabetic cardiomyopathy in male mice

Yandi Wu, Tongsheng Huang, Xinghui Li, Conghui Shen, Honglin Ren, Haiping Wang, Teng Wu, Xinlu Fu, Shijie Deng, Ziqi Feng, Shijie Xiong, Hui Li, Saifei Gao, Zhenyu Yang, Fei Gao, Lele Dong, Jianding Cheng and Weibin Cai ()
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Yandi Wu: Sun Yat-sen University
Tongsheng Huang: Sun Yat-sen University
Xinghui Li: Sun Yat-sen University
Conghui Shen: Sun Yat-sen University
Honglin Ren: Sun Yat-sen University
Haiping Wang: Guangdong Academy of Medical Sciences
Teng Wu: Sun Yat-sen University
Xinlu Fu: Sun Yat-sen University
Shijie Deng: Sun Yat-sen University
Ziqi Feng: Sun Yat-sen University
Shijie Xiong: Sun Yat-sen University
Hui Li: Sun Yat-sen University
Saifei Gao: Sun Yat-sen University
Zhenyu Yang: Sun Yat-sen University
Fei Gao: Durbrain Medical Laboratory
Lele Dong: Durbrain Medical Laboratory
Jianding Cheng: Sun Yat-sen University
Weibin Cai: Sun Yat-sen University

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract Diabetic cardiomyopathy is a primary myocardial injury induced by diabetes with complex pathogenesis. In this study, we identify disordered cardiac retinol metabolism in type 2 diabetic male mice and patients characterized by retinol overload, all-trans retinoic acid deficiency. By supplementing type 2 diabetic male mice with retinol or all-trans retinoic acid, we demonstrate that both cardiac retinol overload and all-trans retinoic acid deficiency promote diabetic cardiomyopathy. Mechanistically, by constructing cardiomyocyte-specific conditional retinol dehydrogenase 10-knockout male mice and overexpressing retinol dehydrogenase 10 in male type 2 diabetic mice via adeno-associated virus, we verify that the reduction in cardiac retinol dehydrogenase 10 is the initiating factor for cardiac retinol metabolism disorder and results in diabetic cardiomyopathy through lipotoxicity and ferroptosis. Therefore, we suggest that the reduction of cardiac retinol dehydrogenase 10 and its mediated disorder of cardiac retinol metabolism is a new mechanism underlying diabetic cardiomyopathy.

Date: 2023
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DOI: 10.1038/s41467-023-36837-x

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