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PTG-Dependent Glycogen Metabolic Dysfunction Drives Impaired Adipose Browning: A Novel Mechanism Linking PM2.5 to
Limin Wang1,2, Renjie Hu1,2, Yanxi Chai1,2
1School of Public Health, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
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.
Insights
Fine particulate matter (PM2.5) impairs adipose tissue browning by disrupting glycogen metabolism via protein targeting to glycogen (PTG). Restoring PTG or activating the ADRB3 receptor counteracts these effects, offering metabolic health targets.
Area of Science:
- Environmental Health
- Metabolic Science
- Adipose Tissue Biology
Background:
- Fine particulate matter (PM2.5) is linked to metabolic dysfunction.
- The specific impact of PM2.5 on adipose tissue browning and the underlying mechanisms are not fully understood.
Purpose of the Study:
- To investigate how PM2.5 affects adipose tissue browning.
- To elucidate the molecular mechanisms, including the role of protein targeting to glycogen (PTG), involved in PM2.5-induced metabolic dysfunction.
Main Methods:
- Exposure of mice to PM2.5.
- Analysis of inguinal white adipose tissue (iWAT) browning, glycogen metabolism, and mitochondrial function.
- Genetic manipulation of PTG and vascular endothelial growth factor B (VEGFB) levels.
- Pharmacological activation of the β3-adrenergic receptor (ADRB3).
Main Results:
- PM2.5 exposure inhibited iWAT browning by downregulating PTG and disrupting glycogen homeostasis.
- Overexpression of PTG reversed PM2.5-induced impairments in browning, thermogenesis, and metabolic disorders.
- PTG negatively regulated VEGFB; VEGFB knockdown rescued browning.
- ADRB3 activation mitigated PM2.5 effects by restoring PTG and normalizing VEGFB.
Conclusions:
- The ADRB3-PTG-VEGFB axis is central to PM2.5-induced metabolic dysfunction.
- Adipose tissue glycogen metabolism is a key target for combating metabolic disruption caused by environmental factors like PM2.5.
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