Nature Communications (Sep 2024)

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,
  • Jurga Laurencikiene

DOI
https://doi.org/10.1038/s41467-024-51938-x
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 18

Abstract

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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.