Hypothesized mechanisms of air pollution–mediated cardiometabolic disease wherein inhalational or nutritional signals either directly or via the generation of signals such as DAMPs may serve to activate innate immune mechanisms such as the TLR and NLR. AP1, activator protein 1; CARD, caspase activation and recruitment domain; IKKb, IκB kinase b; IRAK, interleukin receptor-associated kinase; IRF3, interferon regulatory factor 3; MAPK, mitogen-activated protein kinase; MyD88, myeloid differentiation primary response gene 88; NAFLD, nonalcoholic fatty liver disease; PAMP, pathogen-associated molecular pattern; PAPC, palmitoyl-arachidonyl phosphocholine; RNS, reactive nitrogen species; ROS, reactive oxygen species; TAK, transforming growth factor-β–activated kinase; TBK, TANK-binding kinase 1; TRAF, TNF receptor-associated factor; TRIF, Toll/IL-1 receptor-domain-containing adapter-inducing interferon-β; UCP-1, uncoupling protein-1; WAT, white adipose tissue. Hypothesized mechanisms of air pollution–mediated cardiometabolic disease wherein inhalational or nutritional signals either directly or via the generation of signals such as DAMPs may serve to activate innate immune mechanisms such as the TLR and NLR. AP1, activator protein 1; CARD, caspase activation and recruitment domain; IKKb, IκB kinase b; IRAK, interleukin receptor-associated kinase; IRF3, interferon regulatory factor 3; MAPK, mitogen-activated protein kinase; MyD88, myeloid differentiation primary response gene 88; NAFLD, nonalcoholic fatty liver disease; PAMP, pathogen-associated molecular pattern; PAPC, palmitoyl-arachidonyl phosphocholine; RNS, reactive nitrogen species; ROS, reactive oxygen species; TAK, transforming growth factor-β–activated kinase; TBK, TANK-binding kinase 1; TRAF, TNF receptor-associated factor; TRIF, Toll/IL-1 receptor-domain-containing adapter-inducing interferon-β; UCP-1, uncoupling protein-1; WAT, white adipose tissue. (A high-quality digital representation of this figure is available in the online issue.)‏ Sanjay Rajagopalan, and Robert D. Brook Diabetes 2012;61:3037-3045 ©2012 by American Diabetes Association