Journal article
Liver-derived extracellular vesicles improve whole-body glycaemic control via inter-organ communication
PM Miotto, CH Yang, SN Keenan, W De Nardo, CA Beddows, G Fidelito, GT Dodd, BL Parker, AF Hill, PR Burton, K Loh, MJ Watt
Nature Metabolism | NATURE PORTFOLIO | Published : 2024
Abstract
Small extracellular vesicles (EVs) are signalling messengers that regulate inter-tissue communication through delivery of their molecular cargo. Here, we show that liver-derived EVs are acute regulators of whole-body glycaemic control in mice. Liver EV secretion into the circulation is increased in response to hyperglycaemia, resulting in increased glucose effectiveness and insulin secretion through direct inter-organ EV signalling to skeletal muscle and the pancreas, respectively. This acute blood glucose lowering effect occurs in healthy and obese mice with non-alcoholic fatty liver disease, despite marked remodelling of the liver-derived EV proteome in obese mice. The EV-mediated blood gl..
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Awarded by Gilead Sciences
Funding Acknowledgements
We thank the team at the Ian Holmes Imaging Centre and Melbourne Mass Spectrometry and Proteomics facility of the Bio21 Institute at the University of Melbourne for instrument support, the infrastructure within the Melbourne Murine Metabolic Phenotyping Platform for calorimetry assessment, the Melbourne Histology Platform at the University of Melbourne, M. Shambrook (La Trobe University) for instrument support for the NTA, D. Johnson for technical assistance with running the imaging flow cytometry, and D. Keating (Flinders University) and M. Kebede (University of Sydney) for helpful discussions. P.M.M. was supported by post-doctoral fellowships through the Natural Sciences and Engineering Research Council of Canada (PDF-516731-2018) and Canadian Institutes of Health Research (application no. 430145). This work was supported by a National Health and Medical Research Council (NHMRC) Ideas grant (M.J.W., P.M.M., P.R.B., grant no. APP1184309), NHMRC Investigator grants (P.M.M., grant no. APP2018187; B.J.P., grant no. APP2009642), a Diabetes Australia Research Trust grant (P.M.M.), a Medicine, Dentistry and Health Sciences Early Career Researcher grant (P.M.M., grant no. ECR1782020) and Department of Anatomy and Physiology seed grant (P.M.M.). Graphical illustrations were created with BioRender.com.