White adipose tissue reference network: a knowledge resource for exploring health-relevant relations.

Area of Science:

• Systems biology
• Metabolic health research
• Biomarker discovery

Background:

• Optimal health relies on complex interactions between intrinsic and environmental factors.
• Understanding these interactions is crucial for designing effective health interventions.
• Current approaches often lack a multi-level, integrated view of biological relationships.

Purpose of the Study:

• To introduce the reference network concept for multi-level exploration of biological relations in metabolic health.
• To construct a White Adipose Tissue Health Reference Network (WATRefNet) for biomarker discovery.
• To assess the impact of food and drug compounds on white adipose tissue (WAT) health.

Main Methods:

• Integrated experimental data from 10 studies with seven public molecular interaction databases.
• Incorporated expert definitions of five key WAT health processes: expandability, oxidative capacity, metabolic state, oxidative stress, and inflammation.
• Utilized BIOCLAIMS resource for identifying relevant biomarkers and constructed a network with 6,797 nodes and 32,171 edges.

Main Results:

• Validated the WATRefNet against anti-obesity drug targets, pathology-associated genes, and external disease model data.
• Extracted process-specific subnetworks representing mechanistically supported composite biomarkers.
• Scored five anti-diabetic drug interventions and one diet intervention, confirming lifestyle intervention success and revealing WAT-specific drug effects.

Conclusions:

• The WATRefNet serves as a sustainable knowledge resource for identifying mechanisms of action, nutrient targets, and biomarkers.
• It enables the assessment of health effects for supporting health claims on food products.
• This network facilitates a deeper understanding of interventions impacting WAT health and metabolic status.