Targeted High Performance Liquid Chromatography Tandem Mass Spectrometry-based Metabolomics differentiates metabolic syndrome from obesity

Abstract

We utilized mass spectrometry-based targeted metabolic profiling of 221 metabolites to evaluate the associations between metabolite profiles and established MetS criteria. To our best knowledge, the findings of this study provide the first evidence that metabolic profiles can be used to differentiate participants with MetS from similarly obese individuals who do not meet established criteria of MetS. Furthermore, the study demonstrated that within MetS participants, their unique metabolic profiles correlated to the number of criteria used for MetS determination. Taken together, this metabolic profiling approach can potentially serve as a novel tool for MetS detection and monitoring, and provide useful metabolic information for future interventions targeting obesity and MetS. AbstractBoth obesity and the metabolic syndrome are risk factors for type 2 diabetes and cardiovascular disease. Identification of novel biomarkers are needed to distinguish metabolic syndrome from equally obese individuals in order to direct them to early interventions that reduce their risk of developing further health problems. We utilized mass spectrometry-based targeted metabolic profiling of 221 metabolites to evaluate the associations between metabolite profiles and established metabolic syndrome criteria (i.e. elevated waist circumference, hypertension, elevated fasting glucose, elevated triglycerides, and low high-density lipoprotein cholesterol) in plasma samples from obese men (n ¼ 29; BMI ¼ 35.5 AE 5.2 kg/m 2 ) and women (n ¼ 40; 34.9 AE 6.7 kg/m 2 ), of which 26 met the criteria for metabolic syndrome (17 men and 9 women). Compared to obese individuals without metabolic syndrome, univariate statistical analysis and partial least squares discriminant analysis showed that a specific group of metabolites from multiple metabolic pathways (i.e. purine metabolism, valine, leucine and isoleucine degradation, and tryptophan metabolism) were associated with the presence of metabolic syndrome. Receiver operating characteristic curves generated based on the PLS-DA models showed excellent areas under the curve (0.85 and 0.96, for metabolites only model and enhanced metabolites model, respectively), high specificities (0.86 and 0.93), and good sensitivities (0.71 and 0.91). Moreover, principal component analysis revealed that metabolic profiles can be used to further differentiate metabolic syndrome with 3 versus 4-5 metabolic syndrome criteria. Collectively, these findings support targeted metabolomics approaches to distinguish metabolic syndrome from obesity alone, and to stratify metabolic syndrome status based on the number of criteria met.

Difference in post-stress recovery of the gut microbiome and its altered metabolism after chronic adolescent stress in rats

“…The next-generation sequencing technology, 16S rDNA amplicon sequencing has been widely used in the metagenomic analysis of gut microbiota 23 . LC-MS/MS has also been utilized as the state-of-the-art approach to measure the metabolic composition of biological samples for metabolic profiling studies 24,25 . Interrogation of both the microbial population and metabolites of the intestinal environment using these technical approaches provide valuable insight into gut microbe-host interactions.…”

Targeted metabolic profiling rapidly differentiates Escherichia coli and Staphylococcus aureus at species and strain level

“…A hydrophilic interaction chromatography (HILIC) column was purchased from Waters Corporation (Milford, MA, USA). The chromatographic method was operated as previously described . Analytical grade standard chemical compounds corresponding to the measured metabolites were purchased from Sigma‐Aldrich (St Louis, MO, USA) or IROA Technologies (Boston, MA, USA).…”

“…The targeted metabolic profiling was performed in selected‐reaction monitoring (SRM) mode, established by running multiple standards first, and then using the obtained retention time and SRM transition information to search for the presence of targeted metabolites from unknown samples. Detailed metabolic pathways investigated and metabolites detected have been previously reported and validated . Pooled quality control samples were also run between every ten samples to ensure the performance of the method.…”

“…The mass spectrometry data analysis work flow was similar to our previously published work . Briefly, all raw data were manually inspected using the Quanbrowser module of Xcalibur version 4.0 (Thermo Fisher Scientific).…”

Blood Metabolite Signature of Metabolic Syndrome Implicates Alterations in Amino Acid Metabolism: Findings from the Baltimore Longitudinal Study of Aging (BLSA) and the Tsuruoka Metabolomics Cohort Study (TMCS)

“…Prior work has identified blood serum metabolites that characterize early phenotypes of MetS prior to diagnosis [19]. Metabolomics has also been used to discriminate between overweight and obese individuals with and without MetS [20,21], suggesting some diagnostic utility. Other studies established blood metabolite profiles of different dietary patterns in patients with MetS [22,23], indicating that the approach may be useful for studying the impact of lifestyle on disease processes.…”