BackgroundAnimal studies proved that choline and betaine have beneficial effect on reducing body fat. However, evidence in humans is scarce. We aim to investigate the association between serum choline and betaine levels with body composition in general population.MethodsThis is an observational cross-sectional study performed in 1081 subjects from the CODING (Complex Disease in Newfoundland population: Environment and Genetics) study. Serum choline and betaine levels were measured based on liquid chromatography coupled with tandem mass spectrometry technology. Body composition was measured using dual-energy X-ray absorptiometry following a 12-hour fast. Major confounding factors including age, sex, total calorie intake and physical activity level were controlled in all analyses.ResultsSignificantly inverse correlations were found between serum betaine levels and all obesity measurements in males (r ranged from -0.12 to -0.23, and p<0.01 for all) but not in females. Serum choline was negatively associated with total percent body fat (%BF), percent trunk fat (%TF), weight, body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (r ranged from -0.11 to -0.19, and p<0.05 for all) in males and positively associated with weight, BMI and WC (r ranged from 0.09 to 0.10, and p<0.05 for all) in females. The negative associations between serum choline and betaine levels with obesity in males were more profound in those not on any medication than those taking medications. Moreover, obese males had the lowest serum choline and betaine levels, followed by overweight males, and normal weight males having the highest serum choline and betaine levels, especially in those not taking medications (p<0.05). Likewise, subjects with the highest serum levels of both had the lowest obesity indexes, especially those not taking medications.ConclusionsHigher serum choline and betaine levels were associated with a more favorable body composition (lower body fat and higher lean body mass) in males and the favorable association was more pronounced in non-medication users.

BackgroundSelenoprotein S (SelS) is an important endoplasmic reticulum and plasma membrane-located selenoprotein implicated in inflammatory responses and insulin resistance. However, the effects of SelS on endothelial cells (ECs) have not been reported. In the present study, the role of SelS in oxidative stress and the underlying mechanism were investigated in human ECs.MethodsA SelS over-expression plasmid (pc-SelS) and a SelS-siRNA plasmid were transfected into human umbilical vein endothelial cells (American Type Culture Collection, USA). The cells were divided into four groups: control, SelS over-expression (transfected with pc-SelS), vector control, and SelS knockdown (transfected with siRNA-SelS). After treating the cells with H2O2, the effects of oxidative stress and the expression of caveolin-1 (Cav-1) and protein kinase Cα (PKCα) were investigated.ResultsFollowing treatment with H2O2, over-expression of SelS significantly increased cell viability and superoxide dismutase (SOD) activity, and decreased malondialdehyde (MDA) production and Cav-1 gene and protein expression. However, no effects on PKCα were observed. In contrast, knockdown of SelS significantly decreased cell viability, SOD activity, and PKCα gene and protein expression, and increased MDA production and Cav-1 gene and protein expression.ConclusionsSelS protects ECs from oxidative stress by inhibiting the expression of Cav-1 and PKCα.

Background: We aimed to study the relationships between serum Trimethylamine N-oxide (TMAO) and L-carnitine levels with metabolic syndrome profiles, including obesity, blood pressure, serum lipids, serum glucose and insulin resistance (IR)-related index in humans. Methods: Cross-sectional study was performed in 1,081 subjects from the CODING study in Newfoundland. Serum TMAO and L-carnitine levels were quantified by LC-MS/MS. Metabolic markers were measured in all subjects using fasting blood samples. Partial correlation and linear regression analysis were employed after systematically controlling the major confounding factors, such as age, gender, calorie intake and physical activity level. Results: Serum L-carnitine level was positively correlated with serum triglyceride (TG), serum insulin, IR in males with normal fasting glucose ( p < 0.05 for all) and positively correlated with only serum TG ( p < 0.05) in those with hyperglycemia. In females, significant positive correlations were identified between serum L-carnitine level with obesity, serum total cholesterol, glucose, insulin, and IR in those with normal fasting glucose level ( p < 0.05 for all), while none was found in those with hyperglycemia. Serum TMAO level was only identified to be positively correlated with serum insulin level and IR in hyperglycemic males ( p < 0.05 for all). Conclusions: Serum L-carnitine level was significantly associated with an unfavorable metabolic syndrome (MS) profile mainly in subjects with normal serum glucose level, while serum TMAO level was associated with an unfavorable MS profile in subjects with hyperglycemia. The gender difference warrants further investigations.

Obesity-related insulin resistance is associated with chronic systemic low-grade inflammation, and toll-like receptor 4 (TLR4) regulates inflammation. We investigated the pathways involved in epigallocatechin gallate (EGCG) modulation of insulin and TLR4 signaling in adipocytes. Inflammation was induced in adipocytes by lipopolysaccharide (LPS). An antibody against the 67 kDa laminin receptor (67LR, to which EGCG exclusively binds) was used to examine the effect of EGCG on TLR4 signaling, and a TLR4/MD-2 antibody was used to inhibit TLR4 activity and to determine the insulin sensitivity of differentiated 3T3-L1 adipocytes. We found that EGCG dose-dependently inhibited LPS stimulation of adipocyte inflammation by reducing inflammatory mediator and cytokine levels (IKKβ, p-NF-κB, TNF-α, and IL-6). Pretreatment with the 67LR antibody prevented EGCG inhibition of inflammatory cytokines, decreased glucose transporter isoform 4 (GLUT4) expression, and inhibited insulin-stimulated glucose uptake. TLR4 inhibition attenuated inflammatory cytokine levels and increased glucose uptake by reversing GLUT4 levels. These data suggest that EGCG suppresses TLR4 signaling in LPS-stimulated adipocytes via 67LR and attenuates insulin-stimulated glucose uptake associated with decreased GLUT4 expression.