Metabolomics: a search for biomarkers of visceral fat and liver fat content

Sebastiaan Boone,Renée De Mutsert,Ko Willems Van Dijk,Hildo Lamb,Frits Rosendaal,Martin Den Heijer,Saskia Le Cessie,Albert De Roos,Dennis Mook-Kanamori

doi:10.1007/s11306-019-1599-x

Abstract

IntoductionExcess visceral and liver fat are known risk factors for cardiometabolic disorders. Metabolomics might allow for easier quantification of these ectopic fat depots, instead of using invasive and costly tools such as MRI or approximations such as waist circumference.ObjectiveWe explored the potential use of plasma metabolites as biomarkers of visceral adipose tissue (VAT) and hepatic triglyceride content (HTGC).MethodsWe performed a cross-sectional analysis of a subset of the Netherlands Epidemiology of Obesity study. Plasma metabolite profiles were determined using the Biocrates AbsoluteIDQ p150 kit in 176 individuals with normal fasting plasma glucose. VAT was assessed with magnetic resonance imaging and HTGC with proton-MR spectroscopy. We used linear regression to investigate the associations of 190 metabolite variables with VAT and HTGC.ResultsAfter adjustment for age, sex, total body fat, currently used approximations of visceral and liver fat, and multiple testing, three metabolite ratios were associated with VAT. The strongest association was the lysophosphatidylcholines to total phosphatidylcholines (PCs) ratio [− 14.1 (95% CI − 21.7; − 6.6) cm2 VAT per SD of metabolite concentration]. Four individual metabolites were associated with HTGC, especially the diacyl PCs of which C32:1 was the strongest at a 1.31 (95% CI 1.14; 1.51) fold increased HTGC per SD of metabolite concentration.ConclusionMetabolomics may be a useful tool to identify biomarkers of visceral fat and liver fat content that have added diagnostic value over current approximations. Replication studies are required to validate the diagnostic value of these metabolites.

Highlights

Abdominal obesity, in particular excess visceral adipose tissue and intra-hepatic fat, are well-established risk factors for cardiovascular disease and type 2 diabetes (Tchernof and Despres 2013)
We examined the associations between metabolite concentrations, measured with a commercially available, targeted mass spectrometry-based metabolomics panel, and directly assessed visceral fat by magnetic resonance imaging (MRI) and hepatic triglyceride content measured by proton magnetic resonance spectroscopy (1H-MRS)
Men and women were of similar age and ethnicity, more men had a higher education, men consumed more alcohol, and had a higher body mass index (BMI), waist circumference, hepatic triglyceride content (HTGC) and visceral adipose tissue (VAT), while women had more total body fat than men

Summary

Introduction

In particular excess visceral adipose tissue and intra-hepatic fat, are well-established risk factors for cardiovascular disease and type 2 diabetes (Tchernof and Despres 2013). Easy and inexpensive measurements such as waist circumference (Pouliot et al 1994) or the fatty liver index (Bedogni et al 2006) are often used These methods are vulnerable to misclassification and appear to mainly discriminate between individuals with high or low risk of excess visceral or liver fat (Cuthbertson et al 2014; Tchernof and Despres 2013; Zelber-Sagi et al 2013). With some exceptions (Siegert et al 2013; Szymanska et al 2012) none of these studies examined the diagnostic potential of metabolites over current approximations such as waist circumference

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