Retinol Dehydrogenase 10 Reduction Mediated Retinol Metabolism Disorder Promotes Diabetic Cardiomyopathy in Male Mice

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Mar 2

PMID 36864033

Authors

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

Weibin Cai

Affiliations

Soon will be listed here.

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.

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