Liver-derived extracellular vesicles improve whole-body glycaemic control via inter-organ communication.
Nat Metab
; 6(2): 254-272, 2024 Feb.
Article
em En
| MEDLINE
| ID: mdl-38263317
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 glucose lowering effects were recapitulated by administration of liver EVs derived from humans with or without progressive non-alcoholic fatty liver disease, suggesting broad functional conservation of liver EV signalling and potential therapeutic utility. Taken together, this work reveals a mechanism whereby liver EVs act on peripheral tissues via endocrine signalling to restore euglycaemia in the postprandial state.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Hepatopatia Gordurosa não Alcoólica
/
Vesículas Extracelulares
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Metab
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Austrália