scholarly journals A molecular signature for the metabolic syndrome by urine metabolomics

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Chiara Bruzzone ◽  
Rubén Gil-Redondo ◽  
Marisa Seco ◽  
Rocío Barragán ◽  
Laura de la Cruz ◽  
...  

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.

2021 ◽  
Author(s):  
Chiara Bruzzone ◽  
Rubén Gil-Redondo ◽  
Marisa Seco ◽  
Rocío Barragán ◽  
Laura de la Cruz ◽  
...  

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 (19 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 0.86 and 0.92). 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.


2007 ◽  
Vol 4 (2_suppl) ◽  
pp. S1-S3 ◽  
Author(s):  
Sir George Alberti

Conclusion: The definition of metabolic syndrome needs further refinement and it requires long-term outcome studies to evaluate the various criteria definitively. In general, however, differences of opinion surrounding the syndrome are minor.


Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 979 ◽  
Author(s):  
Eun-Young Kwon ◽  
So Kim ◽  
Myung-Sook Choi

This current study aimed to elucidate the effects and possible underlying mechanisms of long-term supplementation with dietary luteolin (LU)-enriched artichoke leaf (AR) in high-fat diet (HFD)-induced obesity and its complications (e.g., dyslipidemia, insulin resistance, and non-alcoholic fatty liver disease) in C57BL/6N mice. The mice were fed a normal diet, an HFD, or an HFD plus AR or LU for 16 weeks. In the HFD-fed mice, AR decreased the adiposity and dyslipidemia by decreasing lipogenesis while increasing fatty acid oxidation, which contributed to better hepatic steatosis. LU also prevented adiposity and hepatic steatosis by suppressing lipogenesis while increasing biliary sterol excretion. Moreover, AR and LU prevented insulin sensitivity by decreasing the level of plasma gastric inhibitory polypeptide and activity of hepatic glucogenic enzymes, which may be linked to the lowering of inflammation as evidenced by the reduced plasma interleukin (IL)-6, IL-1β, and plasminogen activator inhibitor-1 levels. Although the anti-metabolic syndrome effects of AR and LU were similar, the anti-adiposity and anti-dyslipidemic effects of AR were more pronounced. These results in mice with diet-induced obesity suggest that long-term supplementation with AR can prevent adiposity and related metabolic disorders such as dyslipidemia, hepatic steatosis, insulin resistance, and inflammation.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Manjunath Ramanjaneya ◽  
Jayakumar Jerobin ◽  
Ilham Bettahi ◽  
Kodappully Sivaraman Siveen ◽  
Abdul-Badi Abou-Samra

AbstractObesity and insulin resistance are key elements of the metabolic syndrome, which includes type 2 diabetes (T2D), dyslipidemia, systemic inflammation, hypertension, elevated risk for cardiovascular diseases, non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS). C1Q Tumor necrosis factor-related proteins (CTRPs) have recently emerged as important regulators of metabolism as a core component in the interrelationship between insulin resistance, adiposity and inflammation. To date 15 CTRP members have been identified and most of the CTRPs are dysregulated in obesity, T2D, coronary artery disease and NAFLD. Pharmacological intervention and lifestyle modification alter expression of CTRPs in circulation and in metabolically active tissues. CTRPs enhance metabolism mainly through activation of AMPK/AKT dependent pathways and possess insulin sensitizing properties. Thus dysregulated expression of CTRPs in metabolic disorders could contribute to the pathogenesis of the disease. For these reasons CTRPs appear to be promising targets for early detection, prevention and treatment of metabolic disorders. This review article aims at exploring the role of CTRPs in metabolic syndrome.


Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 270
Author(s):  
Luca Rinaldi ◽  
Pia Clara Pafundi ◽  
Raffaele Galiero ◽  
Alfredo Caturano ◽  
Maria Vittoria Morone ◽  
...  

Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) are two different entities sharing common clinical and physio-pathological features, with insulin resistance (IR) as the most relevant. Large evidence leads to consider it as a risk factor for cardiovascular disease, regardless of age, sex, smoking habit, cholesterolemia, and other elements of MS. Therapeutic strategies remain still unclear, but lifestyle modifications (diet, physical exercise, and weight loss) determine an improvement in IR, MS, and both clinical and histologic liver picture. NAFLD and IR are bidirectionally correlated and, consequently, the development of pre-diabetes and diabetes is the most direct consequence at the extrahepatic level. In turn, type 2 diabetes is a well-known risk factor for multiorgan damage, including an involvement of cardiovascular system, kidney and peripheral nervous system. The increased MS incidence worldwide, above all due to changes in diet and lifestyle, is associated with an equally significant increase in NAFLD, with a subsequent rise in both morbidity and mortality due to both metabolic, hepatic and cardiovascular diseases. Therefore, the slowdown in the increase of the “bad company” constituted by MS and NAFLD, with all the consequent direct and indirect costs, represents one of the main challenges for the National Health Systems.


2011 ◽  
Vol 96 (5) ◽  
pp. 1271-1274 ◽  
Author(s):  
Miriam Hudecova ◽  
Jan Holte ◽  
Matts Olovsson ◽  
Anders Larsson ◽  
Christian Berne ◽  
...  

2010 ◽  
Vol 69 (2) ◽  
pp. 211-220 ◽  
Author(s):  
J. Bernadette Moore

Non-alcoholic fatty liver disease (NAFLD) is now the most common liver disease in both adults and children worldwide. As a disease spectrum, NAFLD may progress from simple steatosis to steatohepatitis, advanced fibrosis and cirrhosis. An estimated 20–35% of the general population has steatosis, 10% of whom will develop the more progressive non-alcoholic steatohepatitis associated with markedly increased risk of cardiovascular- and liver-related mortality. Development of NAFLD is strongly linked to components of the metabolic syndrome including obesity, insulin resistance, dyslipidaemia and type 2 diabetes. The recognition that NAFLD is an independent risk factor for CVD is a major public health concern. There is a great need for a sensitive non-invasive test for the early detection and assessment of the stage of NAFLD that could also be used to monitor response to treatment. The cellular and molecular aetiology of NAFLD is multi-factorial; genetic polymorphisms influencing NAFLD have been identified and nutrition is a modifiable environmental factor influencing NAFLD progression. Weight loss through diet and exercise is the primary recommendation in the clinical management of NAFLD. The application of systems biology to the identification of NAFLD biomarkers and factors involved in NAFLD progression is an area of promising research.


2013 ◽  
Vol 168 (3) ◽  
pp. 393-401 ◽  
Author(s):  
Christa C van Bunderen ◽  
Mirjam M Oosterwerff ◽  
Natasja M van Schoor ◽  
Dorly J H Deeg ◽  
Paul Lips ◽  
...  

ObjectiveHigh as well as low levels of IGF1 have been associated with cardiovascular diseases (CVD). The relationship of IGF1 with (components of) the metabolic syndrome could help to clarify this controversy. The aims of this study were: i) to investigate the association of IGF1 concentration with prevalent (components of) the metabolic syndrome; and ii) to examine the role of (components of) the metabolic syndrome in the relationship between IGF1 and incident CVD during 11 years of follow-up.MethodsData were used from the Longitudinal Aging Study Amsterdam, a cohort study in a representative sample of the Dutch older population (≥65 years). Data were available in 1258 subjects. Metabolic syndrome was determined using the definition of the US National Cholesterol Education Program Adult Treatment Panel III. CVD were ascertained by self-reports and mortality data.ResultsLevels of IGF1 in the fourth quintile were associated with prevalent metabolic syndrome compared with the lowest quintile (odds ratio: 1.59, 95% confidence interval (CI) 1.09–2.33). The middle up to the highest quintile of IGF1 was positively associated with high triglycerides in women. Metabolic syndrome was not a mediator in the U-shaped relationship of IGF1 with CVD. Both subjects without the metabolic syndrome and low IGF1 levels (hazard ratio (HR) 1.75, 95% CI 1.12–2.71) and subjects with the metabolic syndrome and high IGF1 levels (HR 2.28, 95% CI 1.21–4.28) demonstrated increased risks of CVD.ConclusionsIn older people, high-normal IGF1 levels are associated with prevalent metabolic syndrome and high triglycerides. Furthermore, this study suggests the presence of different pathomechanisms for both low and high IGF1 levels and incident CVD.


Sign in / Sign up

Export Citation Format

Share Document