3-adrenergic receptor methylation mediates fine particulate matter inhalation-impaired white adipose tissue browning

Exposure to fine particulate matter (PM2.5), which contains substantial nanoscale particulate matter, induced metabolic disorder. As a critical organ with the potential for energy expenditure induction, inguinal white adipose tissue (iWAT) browning has hardly been examined with exposure to PM2.5 with nanoparticles. This study aimed to explore the effects of ambient PM2.5 exposure on iWAT browning and the underlying mechanisms to gain a deeper understanding of PM2.5 exposure and metabolic disorders. Based on the characterization of the particulate matter, we observed that PM2.5 exposure impaired iWAT browning, accompanied by inhibition of its oxidative phosphorylation, thermogenesis, and inflammation, which induced an increase in fat mass. Then, PM2.5 exposure induced beta 3-adrenergic receptor (ADRB3) gene promoter methylation in the iWAT, followed by decreased ADRB3 expression which was negatively correlated with fat mass. Furthermore, ADRB3 agonist, CL316243, elevated ADRB3 expression by inhibiting DNA methylation. Finally, CL316243 treatment corrected the impaired browning capacity and mitochondrial function in the iWAT of mice exposed to PM2.5. Our findings highlight the importance of Adrb3 DNA methylation-mediated iWAT browning impairment in response to PM2.5 exposure and provide a potential therapeutic target for metabolic dysfunction induced by PM2.5 exposure.