PTG‐Dependent Glycogen Metabolic Dysfunction Drives Impaired Adipose Browning: A Novel Mechanism Linking PM 2.5 to Metabolic Disorders

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.