Mature Adipocyte-Derived Extracellular Vesicles Activate Hepatic Stellate Cells and Promote Liver Fibrosis via Inflammation.

Authors

Venkat Prashanth, Sachin Thomas, Anbarasu Kannan, Madan Kumar Perumal

Published in

Liver international : official journal of the International Association for the Study of the Liver. Volume 46. Issue 11. Pages e70914.

Abstract

Extracellular vesicles (EVs) play a crucial role in intercellular communication, particularly in metabolic regulation and liver disease. This study aimed to investigate the differential effects of EVs derived from pre-adipocytes (PA) and mature adipocytes (MA) on hepatic stellate cell (HSC) activation in vitro and their role in promoting liver fibrosis in high-fat diet (HFD)-fed mice.
EVs were isolated from PA and MA following transdifferentiation, which was confirmed by assessing adipogenic markers (PPAR-γ, perilipin, adiponectin, leptin, and Glut4). EVs were characterized by size and CD9 expression. LX-2 cells were treated with PA- or MA-derived EVs to assess fibrotic and inflammatory gene expression. In vivo, C57BL/6 mice on HFD were administered PA-EVs or MA-EVs to evaluate liver pathology.
MA-EVs exhibited a distinct transcriptomic profile and significantly upregulated fibrotic (α-SMA, COL1A1) and inflammatory markers in LX-2 cells, indicating HSC activation. Conversely, PA-EVs had minimal effects. In HFD-fed mice, MA-EVs injection led to pronounced liver damage, including steatosis, inflammation, and fibrosis, compared with mice receiving PA-EVs, which showed no major pathological changes.
MA-EVs aggravate liver fibrosis and inflammation both in vitro and In vivo, while PA-EVs appear to have relatively limited effects. These findings highlight the functional heterogeneity of adipocyte-derived EVs and suggest MA-EVs as potential contributors to the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). Targeting specific EV subpopulations may present novel therapeutic strategy for MASLD.

PMID:
42865302
Bibliographic data and abstract were imported from PubMed on 13 Oct 2026.

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