IL-1β promotes adipogenesis by directly targeting adipocyte precursors

Kaisa Hofwimmer, Joyce de Paula Souza, Narmadha Subramanian, Milica Vujičić, Leila Rachid, Hélène Méreau, Cheng Zhao, Erez Dror, Emelie Barreby, Niklas K. Björkström, Ingrid Wernstedt Asterholm, Marianne Böni-Schnetzler, Daniel T. Meier (), Marc Y. Donath and Jurga Laurencikiene ()
Additional contact information
Kaisa Hofwimmer: Karolinska Institutet
Joyce de Paula Souza: University of Basel and University Hospital Basel
Narmadha Subramanian: Karolinska Institutet
Milica Vujičić: The Sahlgrenska Academy at University of Gothenburg
Leila Rachid: University of Basel and University Hospital Basel
Hélène Méreau: University of Basel and University Hospital Basel
Cheng Zhao: University of Basel and University Hospital Basel
Erez Dror: University of Basel and University Hospital Basel
Emelie Barreby: Karolinska Institutet, Karolinska University Hospital
Niklas K. Björkström: Karolinska Institutet, Karolinska University Hospital
Ingrid Wernstedt Asterholm: The Sahlgrenska Academy at University of Gothenburg
Marianne Böni-Schnetzler: University of Basel and University Hospital Basel
Daniel T. Meier: University of Basel and University Hospital Basel
Marc Y. Donath: University of Basel and University Hospital Basel
Jurga Laurencikiene: Karolinska Institutet

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Postprandial IL-1β surges are predominant in the white adipose tissue (WAT), but its consequences are unknown. Here, we investigate the role of IL-1β in WAT energy storage and show that adipocyte-specific deletion of IL-1 receptor 1 (IL1R1) has no metabolic consequences, whereas ubiquitous lack of IL1R1 reduces body weight, WAT mass, and adipocyte formation in mice. Among all major WAT-resident cell types, progenitors express the highest IL1R1 levels. In vitro, IL-1β potently promotes adipogenesis in murine and human adipose-derived stem cells. This effect is exclusive to early-differentiation-stage cells, in which the adipogenic transcription factors C/EBPδ and C/EBPβ are rapidly upregulated by IL-1β and enriched near important adipogenic genes. The pro-adipogenic, but not pro-inflammatory effect of IL-1β is potentiated by acute treatment and blocked by chronic exposure. Thus, we propose that transient postprandial IL-1β surges regulate WAT remodeling by promoting adipogenesis, whereas chronically elevated IL-1β levels in obesity blunts this physiological function.

Date: 2024
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DOI: 10.1038/s41467-024-51938-x

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