A molecular signature for the metabolic syndrome by urine metabolomics

Abstract

Background Metabolic syndrome (MetS) is a multimorbid long-term condition without consensual medical definition and a diagnostic based on compatible symptomatology. Here we have investigated the molecular signature of MetS in urine. Methods We used NMR-based metabolomics to investigate a European cohort including urine samples from 11,754 individuals (18–75 years old, 41% females), designed to populate all the intermediate conditions in MetS, from subjects without any risk factor up to individuals with developed MetS (4–5%, depending on the definition). A set of quantified metabolites were integrated from the urine spectra to obtain metabolic models (one for each definition), to discriminate between individuals with MetS. Results MetS progression produces a continuous and monotonic variation of the urine metabolome, characterized by up- or down-regulation of the pertinent metabolites (17 in total, including glucose, lipids, aromatic amino acids, salicyluric acid, maltitol, trimethylamine N-oxide, and p-cresol sulfate) with some of the metabolites associated to MetS for the first time. This metabolic signature, based solely on information extracted from the urine spectrum, adds a molecular dimension to MetS definition and it was used to generate models that can identify subjects with MetS (AUROC values between 0.83 and 0.87). This signature is particularly suitable to add meaning to the conditions that are in the interface between healthy subjects and MetS patients. Aging and non-alcoholic fatty liver disease are also risk factors that may enhance MetS probability, but they do not directly interfere with the metabolic discrimination of the syndrome. Conclusions Urine metabolomics, studied by NMR spectroscopy, unravelled a set of metabolites that concomitantly evolve with MetS progression, that were used to derive and validate a molecular definition of MetS and to discriminate the conditions that are in the interface between healthy individuals and the metabolic syndrome.

Individuals with Metabolic Syndrome Show Altered Fecal Lipidomic Profiles with No Signs of Intestinal Inflammation or Increased Intestinal Permeability

“…Metabolomics may offer a non-invasive, accurate method of screening for both MetS and NAFLD. Metabolomics can analyze and quantify metabolites and lipids linked to metabolic pathways and changes could offer insight into clinical phenotypes [ 88 , 89 , 90 , 91 , 92 , 93 ].…”

“…Mining biofluids such as plasma, serum, urine, and even stool scan help identify biomarkers for diseases. Recently, metabolomic signatures were identified for individuals with MetS using plasma [ 93 ] and urine [ 91 ] biofluids which ultimately provided insight into MetS occurrence and progression. Unlike other biofluids, a stool can also give a comprehensive look into the GI tract as it contains microorganisms, microbial by-products, nutrients such as fibers and lipids, and inflammatory molecules.…”

Towards Multiplexed and Multimodal Biosensor Platforms in Real-Time Monitoring of Metabolic Disorders

“…Biochemical markers are useful indicators for the progression of various health conditions, including stress, infection, and cardio-pulmonary abnormalities [ 9 , 10 , 11 ]. Serial measurements of specific proteins have proven advantageous in determining adverse clinical outcomes and death in critically ill MS patients [ 12 , 13 , 14 ]. However, the blood test is currently the only established and standardized method of measuring these biomarker levels.…”

Lowering of lysophosphatidylcholines in ovariectomized rats by Curcuma comosa

“…These metabolic dysfunctions gradually develop with time. Currently, several omics approaches, such as metabolomics analysis of blood and tissue samples, have been applied to gain new insights into the pathophysiology of metabolic diseases and to evaluate the severity of metabolic disorders and the effectiveness of treatment [ 2 – 4 ].…”