Therapeutic targeting of adipose tissue macrophages ameliorates liver fibrosis in non-alcoholic fatty liver disease.

Celia Martínez-Sánchez,Octavi Bassegoda,Hongping Deng,Xènia Almodóvar,Ainitze Ibarzabal,Ana de Hollanda, Raquel-Adela Martínez García de la Torre,Delia Blaya,Silvia Ariño,Natalia Jiménez-Esquivel,Beatriz Aguilar-Bravo, Julia Vallverdú,Carla Montironi,Oscar Osorio-Conles,Yiliam Fundora, Francisco Javier Sánchez Moreno,Alicia G Gómez-Valadés, Laia Aguilar-Corominas,Anna Soria,Elisa Pose,Adrià Juanola,Marta Cervera,Martina Perez,Virginia Hernández-Gea,Silvia Affò,Kelly S Swanson,Joana Ferrer-Fàbrega,Jose Maria Balibrea,Pau Sancho-Bru,Josep Vidal,Pere Ginès,Andrew M Smith,Isabel Graupera,Mar Coll

JHEP reports : innovation in hepatology（2023）

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摘要

We report that human adipose tissue pro-inflammatory macrophages correlate with hepatic fibrosis in non-alcoholic fatty liver disease (NAFLD). Furthermore, the modulation of adipose tissue macrophages (ATMs) by dextran-nanocarrier conjugated with dexamethasone shifts the pro-inflammatory phenotype of ATMs to an anti-inflammatory phenotype in an experimental murine model of non-alcoholic steatohepatitis. This shift ameliorates adipose tissue inflammation, hepatic inflammation, and fibrosis. Our results highlight the relevance of adipose tissue in NAFLD pathophysiology and unveil ATMs as a potential target for NAFLD.

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关键词

Dextran dexamethasone conjugates,Non-alcoholic steatohepatitis,Liver injury,Adipose tissue inflammation,Nanoparticle,Nanomedicine,Targeted therapy,Drug delivery

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