Constant Benjamin, Kamzolas Ioannis, Yang Xudong, Guo Jingxu, Rodriguez-Fdez Sonia, Mali Iman, Rodriguez-Cuenca Sergio, Petsalaki Evangelia, Vidal-Puig Antonio, Li Wei
Department of Medicine, VPD Heart and Lung Research Institute, School of Clinical Medicine, University of Cambridge, Papworth Road, Cambridge Biomedical Campus, Cambridge, CB2 0BB, UK.
MRC Institute of Metabolic Science, MRC Metabolic Diseases Unit, Addenbrooke's Hospital, University of Cambridge, Box 289, Cambridge, CB2 0QQ, UK.
Sci Rep. 2025 May 8;15(1):15971. doi: 10.1038/s41598-025-99122-5.
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.
脂肪细胞功能障碍会导致脂毒性和心脏代谢疾病。骨形态发生蛋白4（BMP4）在白色脂肪细胞中表达并重塑白色脂肪组织，而肝脏来源的BMP9作为一种关键的循环BMP，会影响脂肪细胞的脂质代谢。成熟脂肪细胞中受BMP4和BMP9信号调控的基因集仍不清楚。在此，我们直接比较了成熟棕色和白色脂肪细胞中的BMP4和BMP9信号。虽然这两种BMP在不同类型的脂肪细胞中表现出相当的效力，但RNA测序分析显示存在广泛的基因调控，白色脂肪细胞中有更多差异表达基因且关键代谢途径受到抑制。尽管BMP4和BMP9在两种脂肪细胞中均诱导了BMP和GDF信号的抑制剂，但它们仅在白色脂肪细胞中选择性地上调了几种TGF-β家族受体和BMP4的表达。这些发现强调了BMP信号在脂肪细胞稳态中的核心作用，并表明BMP4和BMP9均为白色脂肪细胞可塑性的调节因子，具有潜在的治疗意义。
