This study provides the first evidence that PM 2.5 impairs iWAT browning via PTG-mediated glycogen metabolism disruption, which is initiated by ADRB3 inhibition and subsequently triggers VEGFB upregulation. It thereby delineates the ADRB3-PTG-VEGFB axis as central to PM 2.5 -induced metabolic dysfunction and identifies adipose glycogen metabolism as a novel therapeutic target against environmental metabolic disruption. ABSTRACT Fine particulate matter (PM 2.5 ) contributes to metabolic dysfunction, but its effects on adipose tissue browning remain unclear. Here, we showed that PM 2.5 exposure inhibited inguinal white adipose tissue (iWAT) browning by downregulating protein targeting to glycogen (PTG), disrupting glycogen homeostasis. PTG overexpression in iWAT restored glycogen metabolism, thermogenesis, and mitochondrial function, reversing PM 2.5 -induced impairment in iWAT browning and metabolic disorders. Mechanistically, PTG negatively regulated vascular endothelial growth factor B (VEGFB), and VEGFB knockdown rescued browning. Activation of β3-adrenergic receptor (ADRB3) mitigated PM 2.5 ’s effects by restoring PTG and normalizing VEGFB, defining the ADRB3-PTG-VEGFB axis as central to PM 2.5 -induced metabolic dysfunction. Our findings identify adipose glycogen metabolism as a target for countering environmental metabolic disruption.

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Elevated adipocyte-derived AFABP in obesity disrupts iron homeostasis in intestinal stem cells (ISCs), which impairs PPARα signalling and blocks ISC differentiation after injury.