Metabolomic signatures for visceral adiposity and dysglycaemia in Asian Chinese and Caucasian European adults: the cross-sectional TOFI_Asia study

Abstract

Background Asian Chinese are more susceptible to deposition of visceral adipose tissue (VAT) and type 2 diabetes (T2D) development than European Caucasians when matched for gender, age and body mass index (BMI). Our aims were: (i) characterise the ethnicity-specific metabolomic signature of visceral adiposity measured by dual energy X-ray absorptiometry (DXA) and fasting plasma glucose (FPG), and (ii) identify individuals susceptible to worse metabolic health outcomes. Methods Fasting plasma samples from normoglycaemic (n = 274) and prediabetic (n = 83) participants were analysed with liquid chromatography–mass spectrometry using untargeted metabolomics. Multiple linear regression adjusting for age, gender and BMI was performed to identify metabolites associated with FPG and VAT calculated as percentage of total body fat (%VATTBF) in each ethnic group. Metabolic risk groups in each ethnicity were stratified based on the joint metabolomic signature for FPG and %VATTBF and clinically characterised using partial least squares-discriminant analysis (PLS-DA) and t-tests. Results FPG was correlated with 40 and 110 metabolites in Caucasians and Chinese respectively, with diglyceride DG(38:5) (adjusted β = 0.29, p = 3.00E−05) in Caucasians and triglyceride TG(54:4) (adjusted β = 0.28, p = 2.02E−07) in Chinese being the most significantly correlated metabolite based on the p-value. %VATTBF was correlated with 85 and 119 metabolites in Caucasians and Chinese respectively, with TG(56:2) (adjusted β = 0.3, p = 8.25E−09) in Caucasians and TG(58:3) (adjusted β = 0.25, p = 2.34E−08) in Chinese being the most significantly correlated. 24 metabolites associated with FPG were common to both ethnicities including glycerolipid species. 67 metabolites associated with %VATTBF were common to both ethnicities including positive correlations with dihydroceramide, sphingomyelin, glycerolipid, phosphatidylcholine, phosphatidylethnolamine, and inverse correlations with ether-linked phosphatidylcholine. Participant re-stratification found greater total and central adiposity, worse clinical lipid profiles, higher serum glucoregulatory peptides and liver enzymes in normal fasting glucose (NFG) individuals with a prediabetic metabolomic profile than NFG individuals with a normoglycaemic metabolomic profile in both ethnicities. Conclusions Untargeted metabolomics identified common and disparate metabolites associated with FPG and %VATTBF, with an ethnic-dimorphic signature for these metabolic traits. These signatures could improve risk stratification and identify NFG individuals with an adverse cardiometabolic and T2D risk profile.

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“…Metabolites in bold are hub metabolites by degree and betweenness centrality measures. TOFI_Asia study (19), while only a moderate separation of IPFD classes from SVM-RFE ranking metabolites was produced. We set a threshold of ≥ 4.66% as cut point for high IPFD, based on the cohort median, which is 0.16% higher than the weighted mean obtained in a 2017 meta-analysis (38).…”

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“…Metabolite extraction, data acquisition and processing of samples from TOFI_Asia cohort have been previously described [ 25 ]. The processed metabolomic profile from samples in this current MRI cohort were isolated to construct a new dataset for statistical analyses.…”