Visceral adipose tissue area and proportion provide distinct reflections of cardiometabolic outcomes in weight loss; Pooled analysis of MRI-assessed CENTRAL and DIRECT PLUS dietary randomized controlled trials

Background Visceral adipose tissue (VAT) is well established as a pathogenic fat depot, while superficial subcutaneous adipose tissue (SAT) is associated with an improved or no association with the cardiovascular state. However, it is unclear to what extent VAT area (VATcm²) and its proportion of total abdominal adipose tissue (VAT%) are distinguished in predicting cardiometabolic status and clinical outcomes during weight loss. Methods We integrated magnetic resonance imaging (MRI) measurements of VAT, deep-SAT, and superficial-SAT from two 18-month lifestyle weight loss clinical trials, CENTRAL and DIRECT-PLUS (n = 572). Results At baseline, the mean VATcm² was 134.8cm² and VAT%=28.2%; over 18-months, participants lost 28cm² VATcm² (-22.5%), and 1.3 VAT% units. Baseline VATcm² and VAT% were similarly associated with metabolic syndrome, hypertension, and diabetes status, while VAT% better classified hypertriglyceridemia. Conversely, higher VATcm² was associated with elevated high-sensitivity C-reactive protein (hsCRP), while VAT% was not. After 18 months of lifestyle intervention, both VATcm² and VAT% loss were significantly associated with decreased triglycerides, HbA1c, chemerin, ferritin, and liver enzymes, and increased HDL-c levels beyond weight loss (FDR < 0.05). Only VATcm² loss was correlated with decreased HOMA-IR and leptin levels. Conclusions Although increased VATcm² and VAT% exhibit similar clinical manifestations, it might be preferable to examine VAT% when exploring lipid status, while VATcm² may better reflect inflammatory and glycemic states. Trial registration: CENTRAL (Clinical-trials-identifier: NCT01530724); DIRECT-PLUS (Clinical-trials-identifier: NCT03020186)