Hepatic fat is a stronger correlate of key clinical and molecular abnormalities than visceral and abdominal subcutaneous fat in youth.

BMJ Open Diabetes Research & Care
Catherine C CohenMiriam B Vos

Abstract

Body fat distribution is strongly associated with cardiometabolic disease (CMD), but the relative importance of hepatic fat as an underlying driver remains unclear. Here, we applied a systems biology approach to compare the clinical and molecular subnetworks that correlate with hepatic fat, visceral fat, and abdominal subcutaneous fat distribution. This was a cross-sectional sub-study of 283 children/adolescents (7-19 years) from the Yale Pediatric NAFLD Cohort. Untargeted, high-resolution metabolomics (HRM) was performed on plasma and combined with existing clinical variables including hepatic and abdominal fat measured by MRI. Integrative network analysis was coupled with pathway enrichment analysis and multivariable linear regression (MLR) to examine which metabolites and clinical variables associated with each fat depot. The data divided into four communities of correlated variables (|r|>0.15, p<0.05) after integrative network analysis. In the largest community, hepatic fat was associated with eight clinical biomarkers, including measures of insulin resistance and dyslipidemia, and 878 metabolite features that were enriched predominantly in amino acid (AA) and lipid pathways in pathway enrichment analysis (p<0.05). Key meta...Continue Reading

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Citations

Jan 28, 2021·Journal of Clinical Medicine·Amalie LondonKirstine Nyvold Bojsen-Møller
Jul 22, 2021·The Journal of Clinical Endocrinology and Metabolism·Catherine C CohenDana Dabelea

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