Adipose Tissue Depots and Their Cross‐Sectional Associations With Circulating Biomarkers of Metabolic Regulation

BACKGROUND Visceral adipose tissue (VAT) and fatty liver differ in their associations with cardiovascular risk compared with subcutaneous adipose tissue (SAT). Several biomarkers have been linked to metabolic derangements and may contribute to the pathogenicity of fat depots. We examined the association between fat depots on multidetector computed tomography and metabolic regulatory biomarkers. METHODS AND RESULTS Participants from the Framingham Heart Study (n=1583, 47% women) underwent assessment of SAT, VAT, and liver attenuation. We measured circulating biomarkers secreted by adipose tissue or liver (adiponectin, leptin, leptin receptor, fatty acid binding protein 4, fetuin-A, and retinol binding protein 4). Using multivariable linear regression models, we examined relations of fat depots with biomarkers. Higher levels of fat depots were positively associated with leptin and fatty acid binding protein 4 but negatively associated with adiponectin (all P<0.001). Associations with leptin receptor, fetuin-A, and retinol binding protein 4 varied according to fat depot type or sex. When comparing the associations of SAT and VAT with biomarkers, VAT was the stronger correlate of adiponectin (β=-0.28 [women]; β=-0.30 [men]; both P<0.001), whereas SAT was the stronger correlate of leptin (β=0.62 [women]; β=0.49 [men]; both P<0.001; P<0.001 for comparing VAT versus SAT). Although fetuin-A and retinol binding protein 4 are secreted by the liver in addition to adipose tissue, associations of liver attenuation with these biomarkers was not stronger than that of SAT or VAT. CONCLUSIONS SAT, VAT, and liver attenuation are associated with metabolic regulatory biomarkers with differences in the associations by fat depot type and sex. These findings support the possibility of biological differences between fat depots.