Journal article
Estrogen receptor alpha deficiency in cardiomyocytes reprograms the heart-derived extracellular vesicle proteome and induces obesity in female mice
YK Tham, BC Bernardo, B Claridge, GS Yildiz, LML Woon, S Bond, H Fang, JYY Ooi, A Matsumoto, J Luo, CMK Tai, CA Harmawan, H Kiriazis, DG Donner, NA Mellett, ED Abel, SA Khan, DP De Souza, SNE Doomun, K Liu Show all
Nature Cardiovascular Research | SPRINGERNATURE | Published : 2023
Abstract
Dysregulation of estrogen receptor alpha (ERα) has been linked with increased metabolic and cardiovascular disease risk. Here, we generate and characterize cardiomyocyte-specific ERα knockout (ERαHKO) mice to assess the role of ERα in the heart. The most striking phenotype was obesity in female ERαHKO but not male ERαHKO mice. Female ERαHKO mice showed cardiac dysfunction, mild glucose and insulin intolerance and reduced ERα gene expression in skeletal muscle and white adipose tissue. Transcriptomic, proteomic, lipidomic and metabolomic analyses revealed evidence of contractile and/or metabolic dysregulation in heart, skeletal muscle and white adipose tissue. We show that heart-derived extra..
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Awarded by Baker Foundation
Funding Acknowledgements
The authors acknowledge R. Chooi, N. Cemerlang, Y. Alexander, E. Masterman and Y. Liu (Baker Heart and Diabetes Institute) for technical support. This work was supported by the National Heart Foundation of Australia (Grant-In-Aid: ID G 08M 3760 and G 11M 6111 to J.R.M.; Vanguard 105072 to D.G.), National Health and Medical Research Council (NHMRC) project grant (1139489 and 1057741 to D.G.), Future Fund (MRF1201805 to D.G.), Pankind (to D.G.) and the Victorian Government's Operational Infrastructure Support Program. J.R.M. was supported by a NHMRC Senior Research Fellowship (grant no. 1078985) and is supported by a Baker Fellowship. B.C.B. is supported by an Alice Baker and Eleanor Shaw Fellowship (The Baker Foundation, Australia). K.L.W. is supported by a National Heart Foundation Future Leader Fellowship (award ID 102539). B.C. and H.F. are supported by an Australian Government Training Program (RTP) scholarship and Baker Institute Bright Sparks Scholarship Top Up. E.D.A. is supported by the American Heart Association (20SFRN35120123). The metabolomics component of this project used NCRIS-enabled Metabolomics Australia infrastructure at the University of Melbourne and was funded through BioPlatforms Australia. We acknowledge N. Carvajal from the Department of Genomic Medicine at the Alfred Research Alliance for assistance with sequencing.