Nejvíce citovaný článek - PubMed ID 36849732
The artificial sweetener erythritol and cardiovascular event risk
Metabolomics and lipidomics have emerged as tools in understanding the connections of metabolic syndrome (MetS) with cardiovascular diseases (CVD), type 1 and type 2 diabetes (T1D, T2D), and metabolic dysfunction-associated steatotic liver disease (MASLD). This review highlights the applications of these omics approaches in large-scale cohort studies, emphasizing their role in biomarker discovery and disease prediction. Integrating metabolomics and lipidomics has significantly advanced our understanding of MetS pathology by identifying unique metabolic signatures associated with disease progression. However, challenges such as standardizing analytical workflows, data interpretation, and biomarker validation remain critical for translating research findings into clinical practice. Future research should focus on optimizing these methodologies to enhance their clinical utility and address the global burden of MetS-related diseases.
- MeSH
- biologické markery metabolismus MeSH
- diabetes mellitus 1. typu metabolismus komplikace MeSH
- diabetes mellitus 2. typu * metabolismus MeSH
- kardiovaskulární nemoci * metabolismus diagnóza MeSH
- lidé MeSH
- lipidomika * metody MeSH
- metabolický syndrom * metabolismus MeSH
- metabolomika * metody MeSH
- ztučnělá játra metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- biologické markery MeSH
Despite intensive preventive cardiovascular disease (CVD) efforts, substantial residual CVD risk remains even for individuals receiving all guideline-recommended interventions. Niacin is an essential micronutrient fortified in food staples, but its role in CVD is not well understood. In this study, untargeted metabolomics analysis of fasting plasma from stable cardiac patients in a prospective discovery cohort (n = 1,162 total, n = 422 females) suggested that niacin metabolism was associated with incident major adverse cardiovascular events (MACE). Serum levels of the terminal metabolites of excess niacin, N1-methyl-2-pyridone-5-carboxamide (2PY) and N1-methyl-4-pyridone-3-carboxamide (4PY), were associated with increased 3-year MACE risk in two validation cohorts (US n = 2,331 total, n = 774 females; European n = 832 total, n = 249 females) (adjusted hazard ratio (HR) (95% confidence interval) for 2PY: 1.64 (1.10-2.42) and 2.02 (1.29-3.18), respectively; for 4PY: 1.89 (1.26-2.84) and 1.99 (1.26-3.14), respectively). Phenome-wide association analysis of the genetic variant rs10496731, which was significantly associated with both 2PY and 4PY levels, revealed an association of this variant with levels of soluble vascular adhesion molecule 1 (sVCAM-1). Further meta-analysis confirmed association of rs10496731 with sVCAM-1 (n = 106,000 total, n = 53,075 females, P = 3.6 × 10-18). Moreover, sVCAM-1 levels were significantly correlated with both 2PY and 4PY in a validation cohort (n = 974 total, n = 333 females) (2PY: rho = 0.13, P = 7.7 × 10-5; 4PY: rho = 0.18, P = 1.1 × 10-8). Lastly, treatment with physiological levels of 4PY, but not its structural isomer 2PY, induced expression of VCAM-1 and leukocyte adherence to vascular endothelium in mice. Collectively, these results indicate that the terminal breakdown products of excess niacin, 2PY and 4PY, are both associated with residual CVD risk. They also suggest an inflammation-dependent mechanism underlying the clinical association between 4PY and MACE.
