American Diabetes Association
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Loss of hematopoietic cell-derived oncostatin M worsens diet-induced dysmetabolism in mice

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posted on 2023-01-19, 18:55 authored by Mattia Albiero, Stefano Ciciliot, Anna Rodella, Ludovica Migliozzi, Francesco Ivan Amendolagine, Carlotta Boscaro, Gaia Zuccolotto, Antonio Rosato, Gian Paolo Fadini

Innate immune cells infiltrate growing adipose and propagate inflammatory clues to metabolically distant tissues, thereby promoting glucose intolerance and insulin resistance. Cytokines of the IL-6 family and gp130 ligands are among such signals. The role played by Oncostatin M (OSM) in the metabolic consequences of overfeeding is debated at least in part because prior studies did not distinguish OSM sources and dynamics. Here, we explored the role of OSM in metabolic responses and used bone marrow transplantation to test the hypothesis that hematopoietic cells are major contributors to the metabolic effects of OSM. We show that OSM is required to adapt during the development of obesity as OSM concentrations are dynamically modulated during high-fat diet (HFD) and Osm-/- mice displayed early-onset glucose intolerance, impaired muscle glucose uptake, worsened liver inflammation and damage. We found that OSM is mostly produced by blood cells, and that deletion of OSM in hematopoietic cells phenocopied glucose intolerance of whole-body Osm-/- mice on HFD, and recapitulated liver damage with increased aminotransferase levels. We thus uncover that modulation of OSM is involved in the metabolic response to overfeeding and that hematopoietic cell-derived OSM can regulate metabolism, likely via multiple effects in different tissues.


This study was supported by a grant from GlaxoSmithKline, a grant from the University of Padova to MA (Finanziato dall’Unione Europea – NextGenerationEU, STARS@UNIPD MalTraDiates) and a grant to GPF (PNRR M4C2-Investimento 1.4- CN00000041 Finanziato dall’Unione Europea – NextGenerationEU). The external sponsor had no role in the study design, conduction, data analysis, interpretation, and decision to publish.


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