Cell Metabolism——微生物代谢物3-苯基丙酸协调免疫前体细胞相互作用，促进米色脂肪分化与能量消耗

文章地址：https://doi.org/10.1016/j.cmet.2026.01.017

摘要

    Cold exposure induces beige adipogenesis in white adipose tissue, enhancing thermogenesis and energy expenditure. While gut microbiota-derived metabolites influence host metabolism, their role in thermogenic adaptation remains poorly defined. Here, we identify P. copri as a key microbial mediator of cold-induced adipose remodeling. Cold exposure expands P. copri in the colon, which produces 3-phenylpropionic acid (3-PPA), a metabolite that promotes beige adipocyte formation and increases energy expenditure. Mechanis-tically, 3-PPA signals through free fatty acid receptor 1 in M2-like macrophages, inducing chemokine C-X-C motif chemokine 13 (CXCL13) secretion, which recruits T follicular helper cells to facilitate beige adipogen-esis. Lineage-tracing analyses show that adipocyte progenitor cells generate new beige adipocytes in response to 3-PPA. Moreover, 3-PPA supplementation counteracts high-fat diet-induced obesity in mice and promotes thermogenesis in mouse, pig, and human adipose progenitor cells. These findings define a mi-crobiota-immune-adipose progenitor axis regulating cold adaptation and highlight microbial metabolites as potential metabolic therapies.

       低温暴露可诱导白色脂肪组织生成米色脂肪，增强产热和能量消耗。肠道菌群代谢物虽影响宿主代谢，但其在产热适应中的作用尚不明确。本研究发现，P. copri是寒冷诱导脂肪重塑的关键微生物。低温暴露可促进结肠中P. copri的增殖，该菌株产生的代谢物3-苯丙酸（3-PPA）能促进米色脂肪细胞形成并增加能量消耗。其作用机制在于：3-PPA通过M2样巨噬细胞中的游离脂肪酸受体1发挥信号传导，诱导C-X-C趋化因子13（CXCL13）分泌，进而招募滤泡辅助T细胞促进米色脂肪分化。谱系追踪分析表明，脂肪前体细胞在3-PPA刺激下分化为新的米色脂肪细胞。此外，补充3-PPA可缓解小鼠高脂饮食引起的肥胖，并促进小鼠、猪和人类脂肪前体细胞的产热作用。该研究揭示了“菌群-免疫-脂肪前体细胞”轴在调控寒冷适应中的作用，并强调微生物代谢物有望成为代谢性疾病的新疗法。

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