Topographical Body Fat Distribution Links to Amino Acid and Lipid Metabolism in Healthy Non-Obese Women

Visceral adiposity is increasingly recognized as a key condition for the development of obesity related disorders, with the ratio between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) reported as the best correlate of cardiometabolic risk. In this study, using a cohort of 40 obese females (age: 25–45 y, BMI: 28–40 kg/m2) under healthy clinical conditions and monitored over a 2 weeks period we examined the relationships between different body composition parameters, estimates of visceral adiposity and blood/urine metabolic profiles. Metabonomics and lipidomics analysis of blood plasma and urine were employed in combination with in vivo quantitation of body composition and abdominal fat distribution using iDXA and computerized tomography. Of the various visceral fat estimates, VAT/SAT and VAT/total abdominal fat ratios exhibited significant associations with regio-specific body lean and fat composition. The integration of these visceral fat estimates with metabolic profiles of blood and urine described a distinct amino acid, diacyl and ether phospholipid phenotype in women with higher visceral fat. Metabolites important in predicting visceral fat adiposity as assessed by Random forest analysis highlighted 7 most robust markers, including tyrosine, glutamine, PC-O 44∶6, PC-O 44∶4, PC-O 42∶4, PC-O 40∶4, and PC-O 40∶3 lipid species. Unexpectedly, the visceral fat associated inflammatory profiles were shown to be highly influenced by inter-days and between-subject variations. Nevertheless, the visceral fat associated amino acid and lipid signature is proposed to be further validated for future patient stratification and cardiometabolic health diagnostics.

内脏脂肪沉积日益被认为是肥胖相关疾病发生发展的核心危险因素，现有研究表明内脏脂肪组织（visceral adipose tissue, VAT）与皮下脂肪组织（subcutaneous adipose tissue, SAT）的比值是心脏代谢风险（cardiometabolic risk）的最佳关联指标。本研究纳入40名处于健康临床状态的肥胖女性受试者（年龄25~45岁，体质量指数（Body Mass Index, BMI）：28~40 kg/m²），并开展为期2周的跟踪监测，以此分析不同身体成分参数、内脏脂肪沉积评估指标与血液/尿液代谢组特征之间的关联。本研究通过血浆与尿液的代谢组学与脂质组学分析，结合双能X线吸收法（iDXA）与计算机断层扫描（computerized tomography, CT）开展的身体成分及腹部脂肪分布活体定量检测，完成上述关联分析。在多种内脏脂肪评估指标中，VAT/SAT比值与VAT/腹部总脂肪比值均与区域特异性身体瘦体重及脂肪成分存在显著关联。将上述内脏脂肪评估指标与血液、尿液代谢组特征进行整合分析后，可在内脏脂肪水平较高的女性受试者中识别出具有特异性的氨基酸、二酰基磷脂与醚磷脂表型。通过随机森林（Random Forest）分析筛选出的内脏脂肪沉积预测关键代谢物，共得到7个稳定性最优的生物标志物，包括酪氨酸、谷氨酰胺以及PC-O 44∶6、PC-O 44∶4、PC-O 42∶4、PC-O 40∶4与PC-O 40∶3脂质亚型。值得注意的是，与内脏脂肪相关的炎症代谢特征极易受到检测日间差异与受试者个体间差异的影响。尽管如此，与内脏脂肪相关的氨基酸与脂质特征仍有望在未来的患者分层及心脏代谢健康诊断中得到进一步验证与应用。