Dysregulated Metabolic Pathways in Subjects with Obesity and Metabolic Syndrome

Abstract

Background: Obesity coexists with variable features of metabolic syndrome, which is associated with dysregulated metabolic pathways. We assessed potential associations between serum metabolites and features of metabolic syndrome in Arabic subjects with obesity. Methods: We analyzed a dataset of 39 subjects with obesity only (OBO, n = 18) age-matched to subjects with obesity and metabolic syndrome (OBM, n = 21). We measured 1069 serum metabolites and correlated them to clinical features. Results: A total of 83 metabolites, mostly lipids, were significantly different (p < 0.05) between the two groups. Among lipids, 22 sphingomyelins were decreased in OBM compared to OBO. Among non-lipids, quinolinate, kynurenine, and tryptophan were also decreased in OBM compared to OBO. Sphingomyelin is negatively correlated with glucose, HbA1C, insulin, and triglycerides but positively correlated with HDL, LDL, and cholesterol. Differentially enriched pathways include lysine degradation, amino sugar and nucleotide sugar metabolism, arginine and proline metabolism, fructose and mannose metabolism, and galactose metabolism. Conclusions: Metabolites and pathways associated with chronic inflammation are differentially expressed in subjects with obesity and metabolic syndrome compared to subjects with obesity but without the clinical features of metabolic syndrome.

A new framework for exploratory network mediator analysis in omics data

“…Well-established pathways, including insulin secretion ( Seino et al 2011 ), insulin resistance ( Kahn et al 2006 ), and amino sugar and nucleotide sugar metabolism ( Mir et al 2022 ), were discovered as mediator pathways. In addition, our analysis found the links between the nutrition variables to obesity are also mediated by carbohydrate metabolism and lipid metabolism, which has been demonstrated in numerous studies.…”

A multiomic approach to examine the molecular signatures differentiating people with obesity alone from those with obesity and metabolic complications

“…Metabolic biomarkers of gluconeogenesis and glycolysis have also been reported as biomarkers of metabolic syndrome and other cardiometabolic diseases [29]. Several dysregulated microRNAs in OBM (Supplementary table 1.1 and 1.2) involved in glucose metabolism have been previously associated with the metabolic syndrome [30][31][32]. Intriguingly, Mononen et al found a negative association between hsa-miR-93-3p and HbA1c levels, a marker for longstanding dysregulation of glucose metabolism [33].…”

An integrated multi-omic approach demonstrates distinct molecular signatures between human obesity with and without metabolic complications: a case–control study

“…Metabolic biomarkers of gluconeogenesis and glycolysis have also been reported as biomarkers of the metabolic syndrome and other cardiometabolic diseases [ 37 ]. Several dysregulated microRNAs in OBM (Additional file 2 : Tables S1.1 and S1.2) involved in glucose metabolism have been previously associated with the metabolic syndrome [ 38 – 40 ]. Intriguingly, Mononen et al found a negative association between hsa-miR-93-3p and HbA1c levels [ 41 ].…”