Aims. Although obesity is a validated risk factor for metabolic complications and atherosclerotic cardiovascular diseases, a sizeable number of obese individuals do not develop these complications. It is unknown whether inter-individual variation of low-grade inflammation, may underlie atherosclerosis risk in obesity. We hypothesized that differences in inflammation contribute to the risk for atherosclerotic disease in obese individuals.
Methods. We measured a panel of circulating inflammatory markers, some related to the IL-1 family of cytokines, and correlated them to indicators of carotid atherosclerosis  and circulating lipoprotein particles in 302 individuals of European origin with a BMI>27 kg/m2 (300-Obesity cohort). 
Results. We identified IL-18 binding protein (IL-18BP) as a more accurate marker for the presence of carotid atherosclerosis than hsCRP or interleukin-6. IL-18BP correlated strongly with the lipoprotein particles from the very low-density lipoprotein (VLDL) groups and with the number of atherogenic lipoprotein particles (measured by Apolipoprotein B levels). The role of IL-18/IL-18BP pathway in lipoprotein metabolism was validated in IL-18 deficient (IL-18-/-) mice: the absence of IL-18 led to higher plasma triglycerides levels and insulin resistance. The molecular mechanism responsible for the impact on VLDL in the IL-18-/- mice may involve a decreased expression of genes known to be involved in hepatic lipid metabolism including PPP1R3G and ENHO. 
Conclusions. These findings identify IL-18BP as a novel biomarker of atherosclerosis in obese individuals and the IL-18/IL-18BP pathway as functional modulator of VLDL metabolism and atherosclerosis. Future studies should explore the possible diagnostic and treatment approaches based on IL-18/IL-18BP pathway in atherosclerosis.

01 - IL-18 BINDING PROTEIN: A NOVEL BIOMARKER IN OBESITY-RELATED ATHEROSCLEROSIS THAT MODULATES LIPOPROTEIN METABOLISM