Inflammatory Proteomic Network Architecture of Visceral Adiposity and Cardiometabolic Traits
Abstract
Abstract Background : Visceral adipose tissue (VAT) is strongly associated with cardiometabolic disease, but the network architecture connecting visceral adiposity to systemic inflammatory proteins and cardiometabolic traits remains poorly characterized. Methods : We applied an artificial intelligence (AI)-driven network integration approach to plasma inflammatory proteomics (Olink Explore 384) and cardiometabolic traits (VAT, HOMA-IR, glucose, systolic blood pressure [SBP], triglycerides [TG], LDL-C, and HDL-C) in the Vitamin D and Omega-3 Trial (VITAL) discovery cohort (n = 635). Network findings were evaluated for replication in the independent Cocoa Supplement and Multivitamin Outcomes Study (COSMOS) cohort (n = 371). Within-person associations between 2-year changes in proteins and corresponding clinical traits were also evaluated in VITAL. Results : VAT emerged as the central network hub, exhibiting direct connections with multiple cardiometabolic traits and more direct protein connections than any other trait. No inflammatory proteins were directly connected to glucose, HOMA-IR, or SBP in the integrated network; instead, their network connectivity with the inflammatory proteome was dependent on VAT. A triangular network motif linking VAT, HGF, and IL1RN was identified and independently replicated in COSMOS. Longitudinal analyses further showed that 2-year changes in VAT tracked with changes in HGF and IL1RN, while changes in HGF tracked with changes in IL1RN. Overall,…
How strong is the evidence?
Evidence Hub reads this as a cohort study. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 635 participants or records.
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