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Adiponectin receptor 1 variants contribute to hypertrophic cardiomyopathy that can be reversed by rapamycin

Dhandapany, PS and Kang, S and Kashyap, DK and Rajagopal, R and Sundaresan, NR and Singh, R and Thangaraj, K and Jayaprakash, S and Manjunath, CN and Shenthar, J and Lebeche, D (2021) Adiponectin receptor 1 variants contribute to hypertrophic cardiomyopathy that can be reversed by rapamycin. In: Science Advances, 7 (2).

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Official URL: https://dx.doi.org/10.1126/sciadv.abb3991


Hypertrophic cardiomyopathy (HCM) is a heterogeneous genetic heart muscle disease characterized by hypertrophy with preserved or increased ejection fraction in the absence of secondary causes. However, recent studies have demonstrated that a substantial proportion of individuals with HCM also have comorbid diabetes mellitus (~10). Whether genetic variants may contribute a combined phenotype of HCM and diabetes mellitus is not known. Here, using next-generation sequencing methods, we identified novel and ultrarare variants in adiponectin receptor 1 (ADIPOR1) as risk factors for HCM. Biochemical studies showed that ADIPOR1 variants dysregulate glucose and lipid metabolism and cause cardiac hypertrophy through the p38/mammalian target of rapamycin and/ or extracellular signal�regulated kinase pathways. A transgenic mouse model expressing an ADIPOR1 variant displayed cardiomyopathy that recapitulated the cellular findings, and these features were rescued by rapamycin. Our results provide the first evidence that ADIPOR1 variants can cause HCM and provide new insights into ADIPOR1 regulation. Copyright © 2021 The Authors, some rights reserved;

Item Type: Journal Article
Publication: Science Advances
Publisher: American Association for the Advancement of Science
Additional Information: The copyright of this article belongs to American Association for the Advancement of Science
Keywords: Plants (botany), Biochemical studies; Cardiac hypertrophy; Diabetes mellitus; Ejection fraction; Extracellular signals; Hypertrophic cardiomyopathy; Next-generation sequencing; Target of rapamycin, Pathology
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited: 04 Feb 2021 06:19
Last Modified: 04 Feb 2021 06:19
URI: http://eprints.iisc.ac.in/id/eprint/67801

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