2. Academic Validation
  3. PTG-Dependent Glycogen Metabolic Dysfunction Drives Impaired Adipose Browning: A Novel Mechanism Linking PM2.5 to Metabolic Disorders

PTG-Dependent Glycogen Metabolic Dysfunction Drives Impaired Adipose Browning: A Novel Mechanism Linking PM2.5 to Metabolic Disorders

  • Adv Sci (Weinh). 2026 Mar;13(16):e12589. doi: 10.1002/advs.202512589.
Limin Wang 1 2,  Renjie Hu 1 2,  Yanxi Chai 1 2,  Ping He 1 2,  Sanduo Li 1 2,  Lisha Zhao 1 2,  Wenbin Zhao 1 2,  Lu Zhang 1 2,  Li Qin 1 2,  Ran Li 1 2,  Xiaoli Hou 3,  Qinghua Sun 1 2,  Cuiqing Liu 1 2
Affiliations

Affiliations

  • 1 School of Public Health, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
  • 2 Zhejiang International Science and Technology Cooperation Base of Air Pollution and Health, Hangzhou, Zhejiang, China.
  • 3 Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
PMID: 41514494 DOI: 10.1002/advs.202512589
Abstract

Fine particulate matter (PM2.5) contributes to metabolic dysfunction, but its effects on adipose tissue browning remain unclear. Here, we showed that PM2.5 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 PM2.5-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 PM2.5's effects by restoring PTG and normalizing VEGFB, defining the ADRB3-PTG-VEGFB axis as central to PM2.5-induced metabolic dysfunction. Our findings identify adipose glycogen metabolism as a target for countering environmental metabolic disruption.

Keywords

fine particulate matter; glycogen metabolism; iWAT browning; protein targeting to glycogen; vascular endothelial growth factor B; β3‐adrenergic receptor.

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