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Background People commencing a carbohydrate-restricted diet (CRD) experience markedly heterogenous responses in LDL cholesterol, ranging from extreme elevations to reductions. Objectives The aim was to elucidate possible sources of heterogeneity in LDL cholesterol response to a CRD and thereby identify individuals who may be at risk for LDL cholesterol elevation. Methods Hypothesis-naive analyses were conducted on web survey data from 548 adults consuming a CRD. Univariate and multivariate regression models and regression trees were built to evaluate the interaction between body mass index (BMI) and baseline lipid markers. Data were also collected from a case series of five clinical patients with extremely high LDL cholesterol consuming a CRD. Results BMI was inversely associated with LDL cholesterol change. Low triglyceride (TG) to HDL cholesterol ratio, a marker of good metabolic health, predicted larger LDL cholesterol increases. A subgroup of respondents with LDL cholesterol ≥200 mg/dL, HDL cholesterol ≥80 mg/dL, and TG ≤70 mg/dL were characterized as “lean mass hyper-responders.” Respondents with this phenotype (n = 100) had a lower BMI and, remarkably, similar prior LDL cholesterol versus other respondents. In the case series, moderate reintroduction of carbohydrate produced a marked decrease in LDL cholesterol. Conclusions These data suggest that, in contrast to the typical pattern of dyslipidemia, greater LDL cholesterol elevation on a CRD tends to occur in the context of otherwise low cardiometabolic risk., Among adults consuming a carbohydrate-restricted diet, elevated LDL cholesterol was associated with leanness and low triglyceride to HDL cholesterol ratio, contrasting with the typical clinical pattern of atherogenic dyslipidemia., Graphical Abstract Graphical Abstract

Background Regulation of the endoplasmic reticulum (ER) stress pathway is critical to mammary epithelial cell function throughout pregnancy, lactation, and involution. Treatment with trans-10, cis-12 conjugated linoleic acid (t10c12CLA) suppresses mammary lipogenesis and stimulates the ER stress pathway. The ER stress pathway includes tribbles pseudokinase 3 (TRB3), a protein that regulates cellular energy and insulin signaling. Objectives Our objective was to describe the effect of TRB3 deficiency on milk fat synthesis and determine if TRB3 deficiency protects against suppression of mammary lipogenesis. Methods First, mammary Trb3 expression was observed throughout pregnancy and lactation using ancillary microarray data (n = 4/time point). Second, intake, litter growth, and milk clot fatty acid (FA) profile of Trb3 knockout (KO) C57BL/6N mice were compared with wild-type (WT) and heterozygous (HET) mice throughout first (n ≥ 8/group) and second (n ≥ 6/group) lactation. Lastly, the interaction between Trb3 genotype and 2 treatments that suppress mammary lipogenesis, t10c12CLA and high safflower oil (HO) diet, was investigated in a 2 × 2 factorial design (n ≥ 6/group). Results Trb3 expression was higher during late pregnancy and lactation. Trb3 KO and HET mice had lower feed intake, dam weight, and litter growth throughout first, but not second, lactation than WT mice. Treatment with t10c12CLA decreased litter growth (28%; P, This study shows that, although the gene tribbles pseudokinase 3 (Trb3) is upregulated during lactation, it does not play an important role in regulating milk fat synthesis in lactating mice.

Background Postruminal supply of Met during the periparturient period enhances production efficiency (feed conversion to milk) in dairy cows partly through alleviation of oxidant and inflammatory status. Whether alterations in hepatic 1-carbon metabolism (major contributor of antioxidants) and/or energy metabolism contribute to these beneficial effects is unknown. Objectives To investigate alterations in hepatic 1-carbon and energy metabolism and associations with plasma amino acids (AAs) and production efficiency in response to enhanced postruminal supply of Met. Methods Holstein cows (n = 30 per group) were fed during the last 28 d of pregnancy a control diet (CON) or the control plus ethylcellulose rumen-protected Met (MET; 0.9 g/kg of dry matter intake). Plasma (n = 15 per group) and liver tissue (n = 10 per group) were collected throughout the periparturient period to evaluate AA profiles, activity of the tricarboxylic acid cycle, and 1-carbon metabolism via mRNA abundance, enzyme activity, and targeted metabolomics. Results Cows in the MET group had greater overall (27%, P = 0.027) plasma Met concentrations, but had similar total plasma AA concentrations. Although mRNA abundance of 1-carbon metabolism enzymes did not differ, hepatic activity of cystathionine β-synthase (CBS) (51.2 compared with 44.4 mmol/h/mg protein; P = 0.032) and concentration (19%, P = 0.048) of the cellular antioxidant glutathione were greater overall in the MET group. mRNA abundance of aconitase 2 and fumarate hydratase was greater overall (P = 0.049), and phosphoenolpyruvate carboxykinase 1 tended (P = 0.093) to be greater overall in cows fed MET. There was a tendency (P ≤ 0.093) for greater overall hepatic concentrations of malic acid, α-ketoglutaric acid, and isocitric acid in cows fed MET. Conclusions Greater activity of CBS in response to enhanced postruminal supply of Met likely contributes to alleviating oxidant status by increasing concentrations of glutathione. Hence, transsulfuration plays an important role in the observed improvements in production efficiency of dairy cows during the periparturient period.

Background A concern about the excessive consumption of added sugars is the potential for micronutrient dilution, particularly in children and adolescents; however, the evidence is inconsistent. Objective We examined the associations between added sugars intake and micronutrient adequacy in US children and adolescents using data from NHANES 2009–2014. Methods Children and adolescents aged 2–18 (n = 7754), 2–8 (n = 3423), and 9–18 y (n = 4331) were assigned to deciles of added sugars intake based on the average of 2 d of dietary recall. Usual intake of micronutrients was determined using 2 dietary recalls and the National Cancer Institute method. Within each age group, regression analyses were used to assess the relationship between added sugars intake decile and percentage of the population below the estimated average requirements (EARs) for 17 micronutrients. Results Deciles of added sugars intake (percentage of calories) ranged from 22.8 among children and adolescents aged 2–18 y, with a median intake of 13.3% of calories. Significant positive associations (P

Background\ud The periconceptional period is a time in which environmentally induced changes to the epigenome could have significant consequences for offspring health. Metastable epialleles (MEs) are genomic loci demonstrating interindividual variation in DNA methylation with intraindividual crosstissue correlation, suggesting that methylation states are established in the very early embryo before gastrulation. In our previous Gambian studies, we have shown that ME methylation states in the offspring are predicted by maternal concentrations of certain nutritional biomarkers around the time of conception.\ud \ud Objective\ud We aimed to assess whether the profile of maternal biomarker predictors of offspring methylation differs between rainy and dry seasons in a population of rural Gambians, using a larger set of 50 recently identified MEs.\ud \ud Methods\ud We measured 1-carbon biomarkers in maternal plasma back-extrapolated to conception, and cytosine-phosphate-guanine (CpG) methylation at 50 ME loci in their infants’ blood at a mean age of 3.3 mo (n = 120 mother-child pairs). We tested for interactions between seasonality and effects of biomarker concentrations on mean ME methylation z score. We used backward stepwise linear regression to select the profile of nutritional predictors of methylation in each season and repeated this analysis with biomarker principal components (PCs) to capture biomarker covariation.\ud \ud Results\ud We found preliminary evidence of seasonal differences in biomarker-methylation associations for folate, choline, and homocysteine (interaction P values ≤0.03). Furthermore, in stratified analyses, biomarker predictors of methylation changed between seasons. In the dry season, vitamin B-2 and methionine were positive predictors. In the rainy season, however, choline and vitamin B-6 were positive predictors, and folate and vitamin B-12 were negative predictors. PC1 captured covariation in the folate metabolism cycle and predicted methylation in dry season conceptions. PC2 represented the betaine remethylation pathway and predicted rainy season methylation.\ud \ud Conclusions\ud Underlying nutritional status may modify the association between nutritional biomarkers and methylation, and should be considered in future studies.