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<p>Adipocyte dysfunction contributes to lipotoxicity and cardiometabolic diseases. Bone morphogenetic protein 4 (BMP4) is expressed in white adipocytes and remodels white adipose tissue, while liver-derived BMP9, a key circulating BMP, influences adipocyte lipid metabolism. The gene sets regulated by BMP4 and BMP9 signalling in mature adipocytes remain unclear. Here, we directly compare BMP4 and BMP9 signalling in mature brown and white adipocytes. While both BMPs showed comparable potency across adipocyte types, RNA sequencing analysis revealed extensive gene regulation, with many more differentially expressed genes and suppression of critical metabolic pathways in white adipocytes. Although BMP4 and BMP9 induced inhibitors of BMP and GDF signalling in both adipocytes, they selectively upregulated several TGF-β family receptors and BMP4 expression only in white adipocytes. These findings underscore a central role of BMP signalling in adipocyte homeostasis and suggest both BMP4 and BMP9 as regulators of white adipocyte plasticity with potential therapeutic implications.</p>

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Distinct signalling dynamics of BMP4 and BMP9 in brown versus white adipocytes

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年5月8日

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  • Benjamin Constant,
  • Ioannis Kamzolas,
  • Xudong Yang,
  • Jingxu Guo,
  • Sonia Rodriguez-Fdez,
  • Iman Mali,
  • Sergio Rodriguez-Cuenca,
  • Evangelia Petsalaki,
  • Antonio Vidal-Puig,
  • Wei Li

摘要

Adipocyte dysfunction contributes to lipotoxicity and cardiometabolic diseases. Bone morphogenetic protein 4 (BMP4) is expressed in white adipocytes and remodels white adipose tissue, while liver-derived BMP9, a key circulating BMP, influences adipocyte lipid metabolism. The gene sets regulated by BMP4 and BMP9 signalling in mature adipocytes remain unclear. Here, we directly compare BMP4 and BMP9 signalling in mature brown and white adipocytes. While both BMPs showed comparable potency across adipocyte types, RNA sequencing analysis revealed extensive gene regulation, with many more differentially expressed genes and suppression of critical metabolic pathways in white adipocytes. Although BMP4 and BMP9 induced inhibitors of BMP and GDF signalling in both adipocytes, they selectively upregulated several TGF-β family receptors and BMP4 expression only in white adipocytes. These findings underscore a central role of BMP signalling in adipocyte homeostasis and suggest both BMP4 and BMP9 as regulators of white adipocyte plasticity with potential therapeutic implications.