EXPOSURE TO AIR POLLUTION FINE PARTICULATE MATTER (PM2.5) PROMOTES ADIPOSE TISSUE INFLAMMATION AND OBESITY BY IMPAIRING THERMOGENESIS

MARCHINI TIMOTEO; SHEU-TIJANI OLAWALE ABOGUNLOKO; CACERES LOURDES; MARIANA GARCES; VANASCO VIRGINIA; MAGNANI NATALIA; ALVAREZ, SILVIA; EVELSON PABLO; DENNIS WOLF

Congreso; LXVII Reunión anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2022

Clinical evidence suggests that the exposure to air pollution fineparticulate matter (PM2.5) is associated with the development ofcardiometabolic disorders. To study the impact of PM2.5 on inflammation, metabolism, and obesity, male 8-week-old C57BL/6 micereceived 1 mg/kg body weight of a PM2.5 surrogate (ROFA, ResidualOil Fly Ash) or saline (control) by intranasal instillation. ROFA-exposed mice showed a biphasic lung inflammatory cell recruitment,with neutrophils peaking at 6 h and macrophages peaking at 72h, together with significantly increased levels of proinflammatoryTNF-α, IL-6, and CCL2. Bulk mRNA sequencing of sorted alveolarmacrophages from ROFA-exposed mice revealed a proinflammatory gene expression signature and upregulated pathways for redoxand lipid metabolism. Differentially expressed genes, such as CCL3and other inflammatory mediators, were validated by a customizedcytokine bead assay in BAL and plasma, and showed a sustainedincrease for up to 72 h in ROFA-exposed mice. In parallel, decreased metabolic gene expression (Ucp1, Elovl3, Adrb3) in brownadipose tissue suggests reduced lipolysis and thermogenesis, despite ongoing white adipose tissue inflammation. To further explorethis observation, another set of mice were exposed to ROFA or saline and monitored in metabolic cages for 48 h. Despite enhancedphysical activity, ROFA-exposed mice showed significantly reducedheat production. Lastly, consequences of PM2.5 inhalation were evaluated in a real-life mice model of exposure to polluted urban air for16 weeks. Increased weight gain, impaired glucose homeostasis,and adipose tissue inflammation were observed in mice breathingurban air (27±8 µg PM2.5/m3) versus filtered air (2±1 µg PM2.5/m3),together with altered metabolic gene expression in adipose tissue.Our findings indicate that air pollution PM2.5 exposure induce a pulmonary and systemic proinflammatory state that blunts metabolicpathways in adipose tissue and promotes obesity