Fine particulate matter promotes obesity by triggering a systemic inflammatory response that impairs thermogenesis in brown adipose tissue.

MWIYELLA, TIMOTHY; ZIRLIK, ANDREAS; MARCHINI, TIMOTEO; STACHON, PETER; BODE, CHRISTOPH; OLAWALE, TIJANI; HILGENDORF, INGO; WOLF, DENNIS

Ausburgo

Congreso; 2nd Vascular Medicine and Atherosclerosis (VMAC) Congres; 2020

Sociedad Alemana de Cardiología (DGK)

Background: Exposure to air pollution particulate matter (PM) causes 7 million premature deaths worldwide. Cardiovascular disease has been identified as the main complication of airborne fine PM exposure with a diameter of less than 2.5 μm (PM2.5). Epidemiological data also suggest that PM2.5 is associated with Type-2 diabetes mellitus and obesity. However, mechanistic links between air pollution PM2.5 exposure and cardiometabolic disease remain unknown. Methods & Results: Male 8-week-old C57BL/6 mice were exposed to filtered air (FA) or urban air (UA) in whole-body inhalation chambers with PM2.5 levels ranging between 21 and 34 µg/m3 and were fed with a chow diet (10% Kcal fat) or high fat diet (45% Kcal fat) for 16 weeks. Surprisingly, we found that UA-exposed mice on a chow diet weight more, had a greater relative weight gain, and had increased fat accumulation in peripheral fat pads compared to mice breathing FA. This increase ranged at 50% of the weight gain in high-fat diet consuming mice. Functionally, UA-exposed mice showed impaired glucose homeostasis and insulin resistance. To gain further mechanistic insight, we performed an acute exposure with the PM2.5 surrogate (ROFA, Residual Oil Fly Ash) at 1 mg/kg body weight or PBS (control) by intranasal instillation in male 8-week-old C57BL/6 mice. Between 6 and 72 hours after ROFA exposure, we observed biphasic inflammatory cell recruitment into the lungs, with an early increase in neutrophils and Ly6Chigh monocytes and a later rise of lung macrophages. This response was accompanied by gene and protein expression of the pro-inflammatory adipokines TNF-α, IL-6, and MCP-1, as well as by sustained high levels of TNF-α and IL-6 in the plasma of ROFA-exposed mice. In epididymal adipose tissue (epiVAT), we detected increased proinflammatory gene expression (Tnf and Ccl2), together with decreased thermogenic gene expression (Ucp-1, Ppargc1a, and Adrb3) in brown adipose after 24 and 48 hours after the exposure to ROFA, suggesting impaired thermogenesis and an inability to utilize peripheral fat tissue for heart production. Indeed, in metabolic cages, ROFA-exposed mice showed significantly reduced heat production compared to mice on PBS, indicating that PM2.5 exposure has the ability to impair energetic metabolism even after a single exposure.Summary: Our findings indicate that the exposure to air pollution PM2.5 alters energy metabolism and induces obesity, likely as a consequence of local and systemic inflammation. Ultimately, our results highlight the impact of environmental factors in the development of cardiometabolic pathologies in urban areas.