Microbial-derived 3-phenylpropionic acid orchestrates immune-progenitor cell crosstalk to promote beige adipogenesis and energy expenditure.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

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. Mechanistically, 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 adipogenesis. 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 microbiota-immune-adipose progenitor axis regulating cold adaptation and highlight microbial metabolites as potential metabolic therapies.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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