Air pollution modulates brown adipose tissue function through epigenetic regulation by HDAC9 and KDM2B

Area of Science:

• Environmental Health
• Metabolic Disease
• Epigenetics

Background:

• Air pollution is increasingly linked to metabolic disorders like insulin resistance and type 2 diabetes.
• Particulate matter (PM2.5) is a major component of air pollution with known health impacts.

Purpose of the Study:

• To investigate the effects of PM2.5 inhalation on metabolism and brown adipose tissue (BAT) function.
• To elucidate the molecular mechanisms underlying PM2.5-induced metabolic dysfunction in BAT.

Main Methods:

• Whole-body inhalation exposure to concentrated PM2.5 or filtered air for 24 weeks.
• Assessment of glucose uptake using 18F-fluorodeoxyglucose positron emission tomography.
• Analysis of differentially methylated regions, chromatin accessibility, and gene expression in BAT.
• Chromatin immunoprecipitation (ChIP) assays to confirm protein-DNA interactions.

Main Results:

• PM2.5 exposure impaired metabolism and altered BAT function, affecting thermogenesis, redox stress, lipid deposition, and fibrosis.
• Significant differential methylation and chromatin remodeling were observed in BAT following PM2.5 exposure.
• The histone deacetylase HDAC9 and histone demethylase KDM2B were identified as key regulators in PM2.5-induced BAT changes.
• Knockdown of Hdac9/Kdm2b improved BAT metabolism, while overexpression impaired it.

Conclusions:

• PM2.5 exposure induces detrimental epigenetic and transcriptional changes in brown adipose tissue, contributing to metabolic dysfunction.
• HDAC9 and KDM2B play critical roles in mediating the adverse effects of PM2.5 on BAT and overall metabolism.
• These findings provide mechanistic insights into how air pollution contributes to the pathogenesis of insulin resistance and type 2 diabetes.