Investigation into potential mechanisms of metabolic syndrome by integrative analysis of metabolomics and proteomics

Abstract

Metabolic syndrome (MetS) is a complex syndrome cluster of metabolic disorders, which greatly increases the risks of diabetic and cardiovascular diseases. Although it has become a significantly worldwide public health burden, its pathogenesis largely remains unknown. In this study, we first performed an integrated analysis of proteomic and metabonomic data of liver tissues of rats between MetS and control groups to reveal possible mechanisms of MetS. A total of 16 significantly perturbed pathways were identified, of which three pathways were shared by patients with MetS and diabetes identified by analysis of serum samples, including alanine, aspartate and glutamate metabolism, valine, leucine and isoleucine biosynthesis, and glycine, serine and threonine metabolism. Additionally, it was found that 18 differential metabolites were closely related with 36 differential proteins, which were considered as significantly discriminant metabolites and proteins between two groups and were mainly involved in metabolic processes of gamma-aminobutyric acid and acetyl-CoA, biosynthetic processes of cholesterol and amino acids. The results of PPI network analysis and topological parameter calculation of four methods revealed that 16 proteins can serve as hub proteins of MetS. Followed by searching the PubMed database and molecular docking of Cyp7a1 and Got1, we concluded that atorvastatin and resveratrol may be potential drugs for MetS.

Urinary 1H NMR Metabolomic Analysis of Prenatal Maternal Stress Due to a Natural Disaster Reveals Metabolic Risk Factors for Non-Communicable Diseases: The QF2011 Queensland Flood Study

“…Interestingly, many of the pathways involved in the antioxidant response play crucial roles in protein synthesis, energy metabolism, and carbohydrate metabolism. This study found significant alterations in antioxidant metabolic pathways including glutathione metabolism, taurine and hypotaurine metabolism, and ascorbate and aldarate metabolism, suggesting a link between early adverse experiences and the risk of metabolic illness later in life [67][68][69][70].…”

The 40 Hz flickering light restores synaptic plasticity and mitochondrial phenotype in experimental model of Alzheimer’s disease

“…Krebs cycle and glycolysis are two key components inside and outside of the mitochondria, respectively, for energy production in the form of ATP in neurons and other cells [100][101][102]. In addition, the Krebs cycle is the last metabolizing hub for the metabolism of lipids, carbohydrates, and amino acids and is associated with age-related and metabolic diseases [98,101,103]. For example, in the process of aspartate conversion to asparagine, ammonia is transferred from glutamine to asparagine which converts it to glutamate.…”

“…In line with our findings, in a proteomic-metabolomic study of high-sugar-fat diet Wistar rats (an animal model of metabolic syndrome), 16 pathways were enriched. Three pathways were shared by metabolomics studies of serum samples from diabetic patients: 1) alanine, aspartate, and glutamate metabolism, 2) glycine, serine, and threonine metabolism, and 3) valine, leucine, and isoleucine biosynthesis [98]. Transcriptomic and metabolomic joint analysis after an immune challenge with LPS in Zebra fish, revealed enrichment of alanine, aspartate, and glutamate metabolism and aminoacyl-tRNA biosynthesis [99].…”

“…Transcriptomic and metabolomic joint analysis after an immune challenge with LPS in Zebra fish, revealed enrichment of alanine, aspartate, and glutamate metabolism and aminoacyl-tRNA biosynthesis [99]. They reported Krebs cycle was one of the most affected cycles in the mitochondria and highlighted in both studies when analysis was performed by the KEGG pathway [98, 99].…”

Metabolite profiles and DNA methylation in metabolic syndrome: a two-sample, bidirectional Mendelian randomization

“…However, replication of these metabolites across cohorts is lacking, and integration of additional ‘-omics’ data has been recommended to further explicate the pathophysiology of these variations in metabolite levels ( Monnerie et al, 2020 ; Comte et al, 2021 ). For example, an integrative proteomics-metabolomics analysis identified metabolic pathways that were perturbed in the setting of MetS, including serine metabolism ( Chen et al, 2022 ). Another study that combined metabolomic, proteomic, and transcriptomic data showed that mitochondrial respiratory chain dysfunction alters serine biosynthesis pathways ( Bao et al, 2016 ).…”