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.

Abstract

Visceral adipose tissue (VAT) is well established as a pathogenic fat depot, whereas superficial subcutaneous adipose tissue (SAT) is associated with either an improved or neutral 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. 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). At baseline, the mean VATcm² was 144.8cm² 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, ferritin, and liver enzymes, and increased HDL-c levels beyond weight loss (FDR < 0.05). Only VATcm² loss was correlated with decreased HOMA-IR, chemerin, and leptin levels. MRI follow-up of 572 participants over 18 months of weight loss intervention suggests that 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. CENTRAL (Clinical-trials-identifier: NCT01530724); DIRECT PLUS (Clinical-trials-identifier: NCT03020186).