Work

The metabolic organ connectome: A novel approach to measure allostatic load during health-to-disease transition

Year: 2025

Type: article

Abstract: BACKGROUND: F]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) can quantify organ-specific glucose metabolism but is underutilized for inter-organ metabolic analysis. METHODS: We analyzed 658 whole-body FDG-PET scans to construct partial correlation networks (PCNs) reflecting direct metabolic connectivity between organs. We introduced two network metrics, density and disorder, and used them to test PCN robustness to technical and biological factors and to evaluate PCNs as markers for allostatic load (e.g., inflammation or cancer burden). FINDINGS: ) was associated with higher PCN density (33% vs. 14%, p = 0.02) and lower disorder (p = 0.04). Patients with cancer had markedly reduced density (7% vs. 30%, p < 0.001) and higher disorder (p = 0.01) compared to healthy individuals. High C-reactive protein (CRP) and leukocytes were similarly linked to reduced density (6% vs. 12%, p = 0.018, and 6% vs. 10%, p = 0.012, respectively). Elevated norepinephrine was associated with lower density (4% vs. 14%, p = 0.04) and higher disorder (p = 0.12). Networks with low density showed hub formation in skeletal muscle and subcutaneous adipose tissue. PCNs derived from FDG-PET were structurally similar to those based on hexokinase 2 expression (p = 0.01), supporting biological validity. CONCLUSIONS: Whole-body FDG-PET-derived PCNs are a robust, systems-level biomarker of metabolic homeostasis. This method detects early deviations from health and may inform preventive interventions, risk stratification, and therapeutic monitoring. FUNDING: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Source: Med

DOI: 10.1016/j.medj.2025.100881