Figure 4.

Mechanistic framework explaining how inhaled air pollutants disrupt metabolic state. Inhalation of air pollutants (especially particulate matter) can lead to direct activation of alveolar macrophages through TLR2/4-dependent mechanisms and generation of oxidized lipids within lung lining. These oxidized lipids can further activate inflammatory processes through TLR2/4 binding or be released to vasculature, where they will initiate systemic inflammation and oxidative stress responses. TLR2/4-dependent inflammatory activation, through activity of MyD88, will lead to release of proinflammatory cytokines, such as CCL-2 and IL-6, from lung, also generating systemic inflammation. These systemic inflammatory activation processes, along with loss of anti-inflammatory functions from incretins such as GLP-1, will lead to increased recruitment of activated inflammatory cells to tissues and in particular adipose. Recruitment of such cells to adipose will worsen metabolic profile, leading to weight gain and metabolic disease state. Prenatal exposure may enhance cellular and functional responses shown here.