Association of plasma tCys with circulating inflammatory markers, adipokines and insulin-resistance-related parameters.^a

<p>Abbreviations: CRP, C-reactive protein; IL-6, interleukin-6; MCP-1, monocyte chemoattractant protein-1; TNF-α, tumor necrosis factor-alpha; HOMA-IR, homeostasis model assessment of insulin resistance; NEFA, non-esterified fatty acids.</p>a<p>Pearson correlation coefficients, adjusted for the following covariates:</p><p>Model 1: age, gender, plasma methionine, total homocysteine (tHcy) and total glutathione (tGSH).</p><p>Model 2: as in Model 1+ BMI-Z-score.</p><p>Model 3: as in Model 1+ body fat%.</p>b<p>Using log-transformed data.</p

Odds ratios for overweight, obesity and insulin resistance according to plasma total cysteine.

<p>A: Age and gender-adjusted odds ratios and 95% confidence intervals for overweight (white bars) and obesity (grey bars) according to quartiles of plasma total cysteine (tCys). B: Age and gender-adjusted odds ratios for insulin resistance (defined as HOMA-IR index >3.16) by quartiles of plasma tCys, with (grey bars) and without (white bars) adjustment for body fat%. *<i>P</i>≤0.001.</p

Age, body composition and sulfur amino acids.

<p>Dose-response curves (solid lines) with 95% confidence intervals (shaded area) for the association of age with body composition parameters (A) and with plasma concentrations (µmol/L) of methionine, tHcy (total homocysteine), tCys (total cysteine) and tGSH (total glutathione). Figures were constructed using generalized additive regression models in R (see Methods section for details). At approximately mean exposure of the independent variable, the model generates a reference value of zero for the dependent variable. <i>P</i>-values and correlation coefficients were obtained from corresponding Pearson correlation analysis.</p

Association of tCys with body fat%.

<p>Dose-response curves (solid lines) with 95% confidence intervals (shaded area) for the association of plasma tCys with body fat% in normal weight (CDC-BMI percentile <85^th; N = 288) and overweight/obese (CDC BMI percentile ≥85^th; N = 696) children and adolescents after adjustment for age and gender. P-values and partial correlation coefficients were obtained from corresponding linear regression analysis. Data is shown only for the 2.5^th–97.5^th percentiles of tCys for each group.</p

Characteristics of the study population.^a

<p>Abbreviations: OW, overweight; tHcy, total homocysteine; tCys, total cysteine; tGSH, total glutathione; HOMA-IR, homeostasis model assessment of insulin resistance; NEFA, non-esterified fatty acids; CRP, C-reactive protein; IL-6, interleukin-6; MCP-1, monocyte chemoattractant protein-1; TNF-α, tumor necrosis factor-alpha.</p>a<p>Data presented as median (5–95%).</p>b, c<p>Boys significantly different from girls at <i>P</i><0.05 and <i>P</i>≤0.001, respectively.</p>d, e<p>Normal-weight individuals significantly different from overweight/obese subjects within the same gender at <i>P</i><0.05 and <i>P</i>≤0.001, respectively.</p

Exploring the Lean Phenotype of Glutathione-Depleted Mice: Thiol, Amino Acid and Fatty Acid Profiles

<div><p>Background</p><p>Although reduced glutathione (rGSH) is decreased in obese mice and humans, block of GSH synthesis by buthionine sulfoximine (BSO) results in a lean, insulin-sensitive phenotype. Data is lacking about the effect of BSO on GSH precursors, cysteine and glutamate. Plasma total cysteine (tCys) is positively associated with stearoyl-coenzyme A desaturase (SCD) activity and adiposity in humans and animal models.</p><p>Objective</p><p>To explore the phenotype, amino acid and fatty acid profiles in BSO-treated mice.</p><p>Design</p><p>Male C3H/HeH mice aged 11 weeks were fed a high-fat diet with or without BSO in drinking water (30 mmol/L) for 8 weeks. Amino acid and fatty acid changes were assessed, as well as food consumption, energy expenditure, locomotor activity, body composition and liver vacuolation (steatosis).</p><p>Results</p><p>Despite higher food intake, BSO decreased particularly fat mass but also lean mass (both P<0.001), and prevented fatty liver vacuolation. Physical activity increased during the dark phase. BSO decreased plasma free fatty acids and enhanced insulin sensitivity. BSO did not alter liver rGSH, but decreased plasma total GSH (tGSH) and rGSH (by ~70%), and liver tGSH (by 82%). Glutamate accumulated in plasma and liver. Urine excretion of cysteine and its precursors was increased by BSO. tCys, rCys and cystine decreased in plasma (by 23–45%, P<0.001 for all), but were maintained in liver, at the expense of decreased taurine. Free and total plasma concentrations of the SCD products, oleic and palmitoleic acids were decreased (by 27–38%, P <0.001 for all).</p><p>Conclusion</p><p>Counterintuitively, block of GSH synthesis decreases circulating tCys, raising the question of whether the BSO-induced obesity-resistance is linked to cysteine depletion. Cysteine-supplementation of BSO-treated mice is warranted to dissect the effects of cysteine and GSH depletion on energy metabolism.</p></div

Predictors for plasma cobalamin, folate, methylmalonic acid & total homocysteine concentrations among Nepalese children with acute diarrhea in Bhaktapur, Nepal.

<p><i>* Adjusted regression coefficient and P values obtained from linear regression model adjusted for the variables included in this table, R square values of plasma cobalamin, folate, tHcy and MMA are 0.083, 0.30, 0.15 and 0.02, respectively.</i></p

Flow chart of recruitment of children, blood sampling and analysis.

<p>Flow chart of recruitment of children, blood sampling and analysis.</p

Cobalamin and folate concentrations in the study children according to age, gender, breastfeeding status and their metabolic markers.¹

1<p><i>Values are number (%) unless otherwise mentioned</i></p>2<p><i>P values were obtained from Chi-square test or t-test</i></p>3<p><i>Plasma tHcy and MMA were analysed from 819 subject.</i></p

Association between plasma cobalamin and total homocysteine (tHcy) and methylmalonic acid (MMA) concentrations.

<p>The graphs were made by using generalized additive models in R. The upper and lower horizontal lines represent 95% CIs of regression line. The small bars on the x-axis show the distribution of individual observation and the vertical lines indicate the 25^th, 50^th and 75^th percentiles of the plasma cobalamin.</p