Novel associations between inflammation-related proteins and adiposity: a targeted proteomics approach across four population-based studies.

Chronic low-grade inflammation has been proposed as a linking mechanism between obesity and the development of inflammation-related conditions such as insulin resistance and cardiovascular disease. Despite major advances in the last two decades, the complex interplay between immune regulators and obesity remains poorly understood. Therefore, we aimed to identify novel inflammation-related proteins associated with adiposity. We investigated the association between BMI and waist circumference and 72 circulating inflammation-related proteins, measured using the Proximity Extension Assay (Olink Proteomics), in 3,308 participants of four independent European population-based studies (KORA-Fit, BVSII, ESTHER, and Bialystok PLUS). In addition, we used body fat mass measurements obtained by Dual-energy X-ray absorptiometry (DXA) in the Bialystok PLUS study to further validate our results and to explore the relationship between inflammation-related proteins and body fat distribution. We found 14 proteins associated with at least one measure of adiposity across all four studies, including four proteins for which the association is novel: DNER, SLAMF1, RANKL, and CSF-1. We confirmed previously reported associations with CCL19, CCL28, FGF-21, HGF, IL-10RB, IL-18, IL-18R1, IL-6, SCF, and VEGF-A. The majority of the identified inflammation-related proteins were associated with visceral fat as well as with the accumulation of adipose tissue in the abdomen and the trunk. In conclusion, our study provides new insights into the immune dysregulation observed in obesity that might help uncover pathophysiological mechanisms of disease development.