Table 1.

Critical regulators of inflammation in obesity and CVD (50, 52).

	Impact on metabolic function	Impact on atherosclerosis
Free fatty acid	-Contributes ectopic lipid deposition and insulin resistance and type 2 diabetes	-Activates NLRP3 inflammasome and TLR4 in macrophages
IL-6	-Impairs insulin sensitivity and increases T2D risk in genetic analyses	-Secreted by macrophages to further increase inflammation in atheromas
PAI-1	-FFA increases production -Elevated levels found in individuals with abdominal fat accumulation	-Increases risk of intravascular thrombus and CVD by inhibiting tPA and contributing to fibrinolysis and atherothrombosis
TNF-alpha	-Secreted by macrophages in adipose tissue. Implicated in reduced insulin signaling in animal models	-Secreted by macrophages and inflammatory cells in atheromas to further increase inflammation -Causally implicated in CVD in Mendelian randomization analysis

FFA, free fatty acid; IL, interleukin; IR, insulin resistance; PAI-1, plasminogen activator inhibitor-1; T2D, type 2 diabetes; TG, triglycerides; TNF, tumor necrosis factor; tPA, tissue plasminogen activator; WC, waist circumference.