Localized increases in CEPT1 and ATGL elevate plasmalogen phosphatidylcholines in HDLs contributing to atheroprotective lipid profiles in hyperglycemic GCK-MODY

Wang, Xiaojing; Lam, Sin Man; Cao, Mingfeng; Wang, Tong; Wang, Zhixin; Yu, Miao; Li, Bowen; Zhang, Huabing; Ping, Fan; Song, Guangyao; Feng, Kai; Zhang, Qian; Xu, Jianping; Zhou, Liyuan; Deng, Mingqun; Zhai, Xiao; Xiao, Xinhua; Shui, Guanghou

doi:10.1016/j.redox.2021.101855

Cited by 16 publications

(16 citation statements)

References 40 publications

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“…It is postulated that plasmalogens are oxidized in situations of heightened oxidative stress, leading to an upregulation of the biosynthetic pathway. Another study including subjects with Glucokinase-maturity onset diabetes of the young (GCK-MODY) and T2D demonstrated a strong positive associations between serum plasmalogen phosphatidylcholines and total HDL in hyperglycemic individuals [ 53 ]. The authors concluded that in GCK-MODY, HDL-localized increases in the levels of the proteins adipose triglyceride lipase (ATGL) and choline/ethanolamine phosphotransferase 1 (CEPT1) could lead to higher levels of plasmalogen phosphatidylcholines and provide vascular protection against chronic hyperglycemia.…”

Section: Discussionmentioning

confidence: 99%

Plasma metabolomic profiling in subclinical atherosclerosis: the Diabetes Heart Study

Chevli

Freedman

Hsu

et al. 2021

Cardiovasc Diabetol

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Background Incidence rates of cardiovascular disease (CVD) are increasing, partly driven by the diabetes epidemic. Novel prediction tools and modifiable treatment targets are needed to enhance risk assessment and management. Plasma metabolite associations with subclinical atherosclerosis were investigated in the Diabetes Heart Study (DHS), a cohort enriched for type 2 diabetes (T2D). Methods The analysis included 700 DHS participants, 438 African Americans (AAs), and 262 European Americans (EAs), in whom coronary artery calcium (CAC) was assessed using ECG-gated computed tomography. Plasma metabolomics using liquid chromatography-mass spectrometry identified 853 known metabolites. An ancestry-specific marginal model incorporating generalized estimating equations examined associations between metabolites and CAC (log-transformed (CAC + 1) as outcome measure). Models were adjusted for age, sex, BMI, diabetes duration, date of plasma collection, time between plasma collection and CT exam, low-density lipoprotein cholesterol (LDL-C), and statin use. Results At an FDR-corrected p-value < 0.05, 33 metabolites were associated with CAC in AAs and 36 in EAs. The androgenic steroids, fatty acid, phosphatidylcholine, and bile acid metabolism subpathways were associated with CAC in AAs, whereas fatty acid, lysoplasmalogen, and branched-chain amino acid (BCAA) subpathways were associated with CAC in EAs. Conclusions Strikingly different metabolic signatures were associated with subclinical coronary atherosclerosis in AA and EA DHS participants.

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Section: Discussionmentioning

confidence: 99%

Plasma metabolomic profiling in subclinical atherosclerosis: the Diabetes Heart Study

Chevli

Freedman

Hsu

et al. 2021

Cardiovasc Diabetol

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“…Furthermore, PCs have been suggested as a predictive metabolite corresponding with progressive nephropathy [39] and early kidney function declines rapidly in patients with type 1 diabetes [40]. Increased PCs were found in Glucokinase-maturity onset diabetes of the young, which represents a rare genetic disorder due to mutation in the glucokinase (GCK) gene [41]. Recently, PCs showed the strongest correlation with the eye score of NIH, which indicates metabolic dysregulation of tears in ocular chronic graft-versus-host disease [42].…”

Section: Discussionmentioning

confidence: 99%

Metabolomics analysis of plasma identifies aberrant amino acids and lipids metabolism in the patients with acute anterior uveitis

Zhang¹,

xie²,

ma³

et al. 2022

Preprint

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Background Acute anterior uveitis (AAU) is a severe ocular inflammatory disease and the metabolic characteristics are still unclear. To investigate the potential molecular biomarkers and to understand the metabolic response of AAU. Methods Untargeted plasma, which included 181 AAU patients and 99 non-uveitic controls, metabolomics analysis was conducted in this study based on ultra-performance liquid chromatography mass spectrometry (UPLC-MS). Results Eighteen and seven significant changed metabolites were found according to the variable importance in the projection value from orthogonal partial least-squares discriminant analysis (OPLS-DA), p value from univariate analysis and fold change for positive and negative mode, respectively. The AAU metabolomics signature indicated increased 10 amino acids (Glycyltyrosine, Pyroglutamic acid, L-Aspartyl-4-phosphate, Brassica oleracea Alkaloid, L-Glutamic acid, gamma-Glutamyl-S-methylcysteine sulfoxide, Tryptophyl-Glutamine, Diaminopimelic acid, 3-Aminoisobutanoic acid, Glycylproline), 7 lipids (3-Deoxyfructose, Maltitol, PC(20:2(11Z,14Z)/15:0), Cholesterol, PC(22:2(13Z,16Z)/16:1(9Z)), PC(16:1(9Z)/20:0), Cholesterol sulfate), one flavonoids (Quercetin) and two carbohydrates (Sorbitol, N-Acetylneuraminic acid), and decreased 5-Hydroxyindoleacetic acid, L-Histidine, Acetyl-N-formyl-5-methoxykynurenamine, Theophylline and 3-Hydroxybenzoic acid in AAU compare with the control group in both positive and negative modes. Pathway analysis indicated D-Glutamine and D-glutamate metabolism and Histidine metabolism were significantly altered in AAU. Several potential biomarkers for AAU diagnosis were selected by receiver operating characteristic curve (ROC) analysis. Conclusions Our study uncovers a significant difference of plasma metabolic profile for AAU disease. These changes of metabolites in plasma may improve our understanding of the pathophysiology of AAU disease. Further studies are still needed to validate our findings and investigate the function of altered metabolites.

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“…Decreases in CSF and serum APOA1 were observed in patients with schizophrenia [72], and lowered HDL-C was also recorded in major depression [73]. Mechanistic details underlying the neurologically beneficial effects of HDLs have yet to be fully understood, but they might be mediated by the inherent antiinflammatory and antioxidant properties of lipid and/or protein cargoes of HDLs [74,75]. For example, massive remodeling of the HDL proteome upon SARS-CoV-2 infection, such as reduction in paraoxonase 1, renders HDLs from patients with COVID-19 less protective toward endothelial cells stimulated by proinflammatory cytokines compared with controls [76].…”

Section: Trends In Endocrinology and Metabolismmentioning

confidence: 99%

Neurological aspects of SARS-CoV-2 infection: lipoproteins and exosomes as Trojan horses

Lam¹,

Huang²,

Shui³

2022

Trends in Endocrinology & Metabolism

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Localized increases in CEPT1 and ATGL elevate plasmalogen phosphatidylcholines in HDLs contributing to atheroprotective lipid profiles in hyperglycemic GCK-MODY

Cited by 16 publications

References 40 publications

Plasma metabolomic profiling in subclinical atherosclerosis: the Diabetes Heart Study

Plasma metabolomic profiling in subclinical atherosclerosis: the Diabetes Heart Study

Metabolomics analysis of plasma identifies aberrant amino acids and lipids metabolism in the patients with acute anterior uveitis

Neurological aspects of SARS-CoV-2 infection: lipoproteins and exosomes as Trojan horses

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