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Low Serum Choline Concentrations Are Associated with Worse Cognitive Performance in Subjects with Metabolic Syndrome

ABSTRACT: Abstract Objectives Choline is an essential nutrient critical for components of the cell membrane, such as choline-containing phospholipids (phosphatidylcholine and sphingomyelin), and in synthesis of the neurotransmitter acetylcholine. Choline has been shown to exert neuroprotective effects, but the association between serum choline and cognitive performance has been scarcely investigated. Our aims are: 1) To study the association between serum total choline, phosphatidylcholine and sphingomyelin with cognitive performance in subjects with metabolic syndrome; and 2) to analyze genetic variants and dietary intake most associated with cholines in this population. Methods We analyzed 426 subjects (aged 55–75 y) with metabolic syndrome from the PREDIMED Plus-Valencia Study. Serum total choline, phosphatidylcholine and sphingomyelin were determined by NMR spectroscopy. Cognitive tests, including verbal fluency (both semantic and phonemic fluency) and the Trail Making Test (TMT) (parts A and B), were administered. Candidate gene polymorphisms were determined by array genotyping. Diet was analyzed by validated questionnaires. Multivariate regression models were fitted. Results Cholines (total, phosphatidylcholine and sphingomyelin) were strongly associated with sex (higher in women; P < 0.001), age (lower at increasing age; P < 0.05) and diabetes (lower in type-2 diabetics; P < 0.01) in a multivariate model. Although the three tested variables presented statistically significant associations with cognition, serum sphingomyelin was the most associated. Thus, in a multivariate model, serum phosphatidylcholine was directly associated with better verbal fluency (P = 0.040 and P = 0.029 for phonemic and semantic, respectively) and inversely associated (lower score mean better performance) with the TMT-A (P = 0.013) and the TMT-B (P = 0.035). In the genetic analysis, we detected several polymorphisms strongly associated with cholines (rs10991629-SLC44A1 with P < 0.005 and rs8068641-PEMT; P < 0.01, among others). We identified several dietary associations as well as gene-diet modulations. Conclusions Phosphatidylcholines are associated with better cognitive function and their levels are modulated by diet and genetics. Funding Sources Generalitat Valenciana (PROMETEO2017/017) and Spanish Ministry of Science (FPU 18/0,1703).

SUBMITTER: Coltell O

PROVIDER: S-EPMC7258305 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Project description:Introduction: Zinc-?2-glycoprotein (ZAG) is a novel adipokine, which is involved in metabolic syndrome (MetS). This study aimed to investigate the relationship between serum ZAG and MetS in Chinese adults, who diagnosed according to the 2005 International Diabetes Federation (IDF) criteria. Methods: A group of 151 MetS patients, 84 patients with central obesity and 70 healthy controls were enrolled. General clinical information, serum samples were obtained from all subjects and serum ZAG levels were determined via the commercial ELISA kits. Results: Serum ZAG levels were the highest in the control group, then gradually decreased with the severity of the metabolic abnormalities increased (8.78 ± 1.66 ?g/mL for control vs. 8.37 ± 1.52 ?g/mL for central obesity vs. 7.98 ± 0.94 ?g/mL for MetS, P < 0.05). It was also decreased progressively with an increasing number of the MetS components (P for trend = 0.002). Additionally, serum ZAG/fat mass ratio was calculated and the similar changes were observed in the three groups (0.85 ± 0.53 ?g/mL/kg for control vs. 0.39 ± 0.10 ?g/mL/kg for central obesity vs. 0.36 ± 0.08 ?g/mL/kg for MetS, P < 0.05). In the multiple regression analysis, group was a strong independent factor contributing to serum ZAG levels (P < 0.001). Furthermore, compared with subjects with the highest tertile of ZAG, subjects in the lowest tertile of ZAG had 1.946-fold higher risk of MetS (95% CI 1.419-6.117, P = 0.004). This phenomenon still existed after controlling for age, gender (Model 1), ALP, AST, Cr, UA, Urea based on Model 1 (Model 2), grip strength, smoking, drinking, birth place, current address, education level, manual labor, and exercise frequency based on Model 2 (Model 3). Receiver operation characteristic (ROC) curve analysis revealed that serum ZAG might serve as a candidate biomarker for MetS (sensitivity 57.6%, specificity 70.0% and area under the curve 0.655), and serum ZAG/fat mass ratio showed improved diagnosis value accuracy, with ROC curve area of 0.951 (95% CI, 0.920-0.983, P < 0.001), and 90.7% sensitivity and 88.6% specificity. Conclusions: Serum ZAG levels were lowered in patients with MetS and central obesity. The decreased serum ZAG levels were associated with the increased risks of MetS. Serum ZAG, especially serum ZAG/fat mass ratio might be the candidate diagnostic biomarkers for MetS.

Project description:Emerging evidence has consistently shown that a very low carbohydrate diet (VLCD) can protect against the development of obesity, but the underlying mechanisms are not fully understood. Here we applied a comprehensive metabonomics approach using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry and gas chromatography-time-of-flight mass spectrometry to study the effects of an 8-week dietary intervention with VLCD on serum metabolic profiles in obese subjects. The VLCD intervention resulted in a weight loss and significantly decreased homeostasis model assessment-insulin resistance. The metabonomics analysis identified a number of differential serum metabolites (p < 0.05) primarily attributable to fatty acids, amino acids including branched chain amino acids, amines, lipids, carboxylic acids, and carbohydrates in obese subjects compared to healthy controls. The correlation analysis among time, VLCD intervention, and clinical parameters revealed that the changes of metabolites correlated with the changes of clinical parameters and showed differences in males and females. Fatty acids, amino acids, and carboxylic acids were increased in obese subjects compared with their normal healthy counterparts. Such increased levels of serum metabolites were attenuated after VLCD intake, suggesting that the health beneficial effects of VLCD are associated with attenuation of impaired fatty acid and amino acid metabolism. It also appears that VLCD induced significant metabolic alterations independent of the obesity-related metabolic changes. The altered metabolites in obese subjects post-VLCD intervention include arachidonate, cis-11,14-eicosadienoate, cis-11,14,17-eicosatrienoate, 2-aminobutyrate, acetyl-carnitine, and threonate, all of which are involved in inflammation and oxidation processes. The results revealed favorable shifts in fatty acids and amino acids after VLCD intake in obese subjects, which should be considered biomarkers for evaluating health beneficial effects of VLCD and similar dietary interventions.

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Low Serum Choline Concentrations Are Associated with Worse Cognitive Performance in Subjects with Metabolic Syndrome

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