IL-1β promotes adipogenesis by directly targeting adipocyte precursors

Nat Commun. 2024 Sep 11;15(1):7957. doi: 10.1038/s41467-024-51938-x.

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.

MeSH terms

  • Adipocytes* / cytology
  • Adipocytes* / metabolism
  • Adipogenesis* / drug effects
  • Adipogenesis* / genetics
  • Adipose Tissue, White* / cytology
  • Adipose Tissue, White* / metabolism
  • Animals
  • CCAAT-Enhancer-Binding Protein-beta* / genetics
  • CCAAT-Enhancer-Binding Protein-beta* / metabolism
  • CCAAT-Enhancer-Binding Protein-delta / genetics
  • CCAAT-Enhancer-Binding Protein-delta / metabolism
  • Cell Differentiation / drug effects
  • Humans
  • Interleukin-1beta* / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Interleukin-1 Type I* / genetics
  • Receptors, Interleukin-1 Type I* / metabolism
  • Stem Cells / drug effects
  • Stem Cells / metabolism

Substances

  • Interleukin-1beta
  • Receptors, Interleukin-1 Type I
  • CCAAT-Enhancer-Binding Protein-beta
  • CCAAT-Enhancer-Binding Protein-delta
  • IL1R1 protein, mouse
  • Cebpd protein, mouse
  • Cebpb protein, mouse
  • IL1B protein, mouse