Dietary intake, plasma homocysteine, and repetitive element DNA methylation in the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: DNA methylation of repetitive elements may explain the relations between dietary intake, hyperhomocysteinemia, and cardiovascular disease risk. We investigated associations of methyl micronutrient intake and plasma total homocysteine with LINE-1 and Alu methylation in a cross-sectional study of 987 adults aged 45-84 y who participated in the Multi-Ethnic Study of Atherosclerosis (MESA) Stress Study. METHODS AND RESULTS: DNA methylation was estimated using pyrosequencing technology. A 120-item food frequency questionnaire was used to ascertain daily intake of folate, vitamin B12, vitamin B6, zinc, and methionine. Plasma total homocysteine was quantified using a fluorescence polarization immunoassay. Associations of micronutrient intake and homocysteine with LINE-1 and Alu methylation were examined using linear regression. Adjusted differences in %5-methylated cytosines (%5 mC) were examined by categories of predictors using multivariable linear regression models. Intake of methyl-donor micronutrients was not associated with DNA methylation. After adjustment for covariates, each 3 µmol/L increment of homocysteine corresponded with 0.06 (-0.01, 0.13) %5 mC higher LINE-1 methylation. Additionally, BMI was positively associated with LINE-1 methylation (P trend = 0.03). Participants with BMI ≥ 40 kg/m² had 0.35 (0.03, 0.67) %5 mC higher LINE-1 than those with normal BMI. We also observed a 0.10 (0.02, 0.19) %5 mC difference in Alu methylation per 10 cm of height. These associations did not differ by sex. CONCLUSION: Dietary intake of methyl-donor micronutrients was not associated with measures of DNA methylation in our sample. However, higher BMI was related to higher LINE-1 methylation, and height was positively associated with Alu methylation.

Lipoprotein receptor-related protein 1 variants and dietary fatty acids: meta-analysis of European origin and African American studies.

OBJECTIVE: Low-density lipoprotein-related receptor protein 1 (LRP1) is a multi-functional endocytic receptor and signaling molecule that is expressed in adipose and the hypothalamus. Evidence for a role of LRP1 in adiposity is accumulating from animal and in vitro models, but data from human studies are limited. The study objectives were to evaluate (i) relationships between LRP1 genotype and anthropometric traits, and (ii) whether these relationships were modified by dietary fatty acids. DESIGN AND METHODS: We conducted race/ethnic-specific meta-analyses using data from 14 studies of US and European whites and 4 of African Americans to evaluate associations of dietary fatty acids and LRP1 genotypes with body mass index (BMI), waist circumference and hip circumference, as well as interactions between dietary fatty acids and LRP1 genotypes. Seven single-nucleotide polymorphisms (SNPs) of LRP1 were evaluated in whites (N up to 42 000) and twelve SNPs in African Americans (N up to 5800). RESULTS: After adjustment for age, sex and population substructure if relevant, for each one unit greater intake of percentage of energy from saturated fat (SFA), BMI was 0.104 kg m(-2) greater, waist was 0.305 cm larger and hip was 0.168 cm larger (all P<0.0001). Other fatty acids were not associated with outcomes. The association of SFA with outcomes varied by genotype at rs2306692 (genotyped in four studies of whites), where the magnitude of the association of SFA intake with each outcome was greater per additional copy of the T allele: 0.107 kg m(-2) greater for BMI (interaction P=0.0001), 0.267 cm for waist (interaction P=0.001) and 0.21 cm for hip (interaction P=0.001). No other significant interactions were observed. CONCLUSION: Dietary SFA and LRP1 genotype may interactively influence anthropometric traits. Further exploration of this, and other diet x genotype interactions, may improve understanding of interindividual variability in the relationships of dietary factors with anthropometric traits.

Transferability and fine-mapping of glucose and insulin quantitative trait loci across populations: CARe, the Candidate Gene Association Resource.

AIMS/HYPOTHESIS: Hyperglycaemia disproportionately affects African-Americans (AfAs). We tested the transferability of 18 single-nucleotide polymorphisms (SNPs) associated with glycaemic traits identified in European ancestry (EuA) populations in 5,984 non-diabetic AfAs. METHODS: We meta-analysed SNP associations with fasting glucose (FG) or insulin (FI) in AfAs from five cohorts in the Candidate Gene Association Resource. We: (1) calculated allele frequency differences, variations in linkage disequilibrium (LD), fixation indices (F(st)s) and integrated haplotype scores (iHSs); (2) tested EuA SNPs in AfAs; and (3) interrogated within ± 250 kb around each EuA SNP in AfAs. RESULTS: Allele frequency differences ranged from 0.6% to 54%. F(st) exceeded 0.15 at 6/16 loci, indicating modest population differentiation. All iHSs were <2, suggesting no recent positive selection. For 18 SNPs, all directions of effect were the same and 95% CIs of association overlapped when comparing EuA with AfA. For 17 of 18 loci, at least one SNP was nominally associated with FG in AfAs. Four loci were significantly associated with FG (GCK, p = 5.8 × 10(-8); MTNR1B, p = 8.5 × 10(-9); and FADS1, p = 2.2 × 10(-4)) or FI (GCKR, p = 5.9 × 10(-4)). At GCK and MTNR1B the EuA and AfA SNPs represented the same signal, while at FADS1, and GCKR, the EuA and best AfA SNPs were weakly correlated (r(2) <0.2), suggesting allelic heterogeneity for association with FG at these loci. CONCLUSIONS/INTERPRETATION: Few glycaemic SNPs showed strict evidence of transferability from EuA to AfAs. Four loci were significantly associated in both AfAs and those with EuA after accounting for varying LD across ancestral groups, with new signals emerging to aid fine-mapping.

"No-one realises what we go through as Type 1s": A qualitative photo-elicitation study on coping with diabetes.

AIMS: Type 1 diabetes (T1D) has physical, emotional, and social consequences and little is known how adults cope with the condition long term. This research aimed to use a novel photo-elicitation technique to gain in-depth insight into the personal coping experiences of adults living with T1D. METHODS: In-depth photo elicitation interviews were employed to collect data and transcripts were analysed using thematic analysis. RESULTS: Participant-led data revealed an overarching theme of the relentlessness of the condition. Continuous self-management tasks infiltrated participants' lives and had a significant impact on coping experiences. A range of techniques and resources were used to cope including using alarms and reminders, diabetes technology, interpersonal relationships, supportive healthcare services and seeking a mind-body balance. CONCLUSIONS: Technology shows promise for easing the burden of the condition, expert-led online support would be of benefit, and peer support should be prioritised within interventions for adults with T1D.

Consumption of isoflavone-rich soy protein does not alter homocysteine or markers of inflammation in postmenopausal women.

BACKGROUND/OBJECTIVE: To investigate the effect of soy protein containing isoflavones on homocysteine (Hcy), C-reactive protein (CRP), soluble E-selectin (sE-selectin), soluble vascular adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1). SUBJECT/METHODS: In a randomized crossover design, 34 postmenopausal women consumed soy protein isolate (26+/-5 g protein containing 44+/-8 mg isoflavones per day) or milk protein isolate (26+/-5 g protein per day) for 6 weeks each. Fasting blood samples were collected at the end of each diet period and end points analyzed by enzyme-linked immunosorbent assay. RESULTS: Concentrations of Hcy, CRP, sE-selectin, sVCAM-1 and sICAM-1 were not different between soy and milk diet treatments. Results did not differ by equol production status or by baseline lipid concentration. Adjustment for intake of folate and methionine did not alter the Hcy results. CONCLUSIONS: These data suggest that decreasing vascular inflammation and Hcy concentration are not likely mechanisms by which soy consumption reduces coronary heart disease risk.

Protein-energy interrelationships during dietary restriction: effects on tissue nitrogen and protein turnover.

Young adult female rats were fed diets containing either 50 or 0% lactalbumin at levels of 2, 4 or 6 g diet/day for 2, 8, and 16 days. There was no other protein in the diet. Tissue nitrogen and loss of radioactivity from tissues labeled with 14C- and 3H-glutamate were measured. In a second study, similar rats were fed graded levels of lactalbumin at food intake levels of 3, 5, or 7 g/day. Change in tissue nitrogen varied with the tissue, the time of observation, and the severity of the food restriction. After 8 days, animals fed high levels of protein at the most severe food restriction showed increases in gastrocnemius nitrogen and losses in liver nitrogen, while after 16 days both tissues had marked nitrogen losses. Nitrogen losses at the lowest level of food intake increased with the dietary protein level, whereas dietary protein was protective of tissue nitrogen at higher food intakes. Severity of energy restriction had no effect on loss of tissue radioactivity and the apparently longer tissue protein half-lives from animals fed protein-free diets are attributed to increased amino acid recycling. Such results indicate that short-term studies and overall nitrogen balance experiments will fail to identify changes occurring in different tissues and may yield misleading results.

Are n-3 fatty acids essential nutrients for fetal and infant development?

Recent research indicates that n-3 fatty acids (FAs) are essential nutrients in early human development. In human infants, nonhuman primates, and animal models, the n-3 FA, docosahexaenoic acid (DHA, 22:6n-3) is highly concentrated in brain and retinal tissues and accumulates during late fetal and early neonatal life. Diets deficient in n-3 FAs are associated with reduced levels of DHA in erythrocytes and brain and retinal tissues and with abnormalities in retinal function that may be irreversible. The precursor of DHA, alpha-linolenic acid (LNA, 18:3n-3), may be an inadequate substitute for DHA because LNA may not be converted to DHA in sufficient amounts to meet an infant's needs. Premature infants lose DHA from their tissues unless they are fed human milk or formula supplemented with DHA. Fish and shellfish are the main food sources of DHA. Women who consume fish have more DHA in their breast milk than do those who do not eat seafood. Infant formulas contain only LNA as a source of n-3 FAs. Pregnant and nursing women should be encouraged to consume seafood on a regular basis during pregnancy and lactation to furnish DHA for their infants.

Omega-3 fatty acids: comparison of plant and seafood sources in human nutrition.

Omega-3 Fatty acids (omega-3FAs) are found in seafoods, some plants, and some livestock rations. Fish oils are the only concentrated source of eicosapentaenoic acid (EPA; 20:5 omega-3) and docosahexaenoic acid (DHA; 22:6 omega-3). The major omega-3FA in plants is alpha-linolenic acid (LNA; 18:3 omega-3). LNA must be converted to EPA before it exerts biological effects similar to EPA, such as reduced platelet aggregation. Human beings convert LNA to EPA to a small extent only. LNA may be more readily oxidized than incorporated into tissues. The effects of consuming LNA-rich oils are more modest than the effects of EPA-rich oils. Evidence suggests that omega-3FAs are essential and highly desirable for brain and eye development and heart health. LNA is the only source of omega-3FAs for vegetarians. Because LNA and EPA are not biologically equivalent, food composition data or product claims mentioning total omega-3FA content must clarify the individual omega-3FAs present.

Ethnicity, plasma phospholipid fatty acid composition and inflammatory/endothelial activation biomarkers in the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND/OBJECTIVES: It has been recognized that certain long-chain polyunsaturated fatty acids (LC-PUFAs) are involved in inflammation and its resolution. It has also been shown that ethnicity may be a factor in affecting systemic inflammation, and limited evidence suggests it may influence plasma LC-PUFA composition. Given the links among these three factors, we aim to determine ethnicity-based differences in plasma LC-PUFA composition among White, Black, Hispanic and Chinese participants, and whether such differences contribute to variations in markers of inflammation and endothelial activation in a sub-cohort of the Multi-Ethnic Study of Atherosclerosis (MESA). SUBJECTS/METHODS: Plasma phospholipid LC-PUFAs levels (%) were determined in 2848 MESA participants using gas chromatography-flame ionization detection. Enzyme immunoassays determined inflammatory markers levels for high-sensitivity C-reactive protein (n=2848), interleukin-6 (n=2796), soluble tumor necrosis factor-α receptor type 1 (n=998), and endothelial activation markers soluble intercellular adhesion molecule-1 (n=1192) and soluble E-selectin (n=998). The modifying influence of ethnicity was tested by linear regression analysis. RESULTS: Chinese adults were found to have the highest mean levels of plasma eicosapentaenoic acid (EPA, 1.24%) and docosahexaenoic acid (DHA, 4.95%), and the lowest mean levels of γ-linolenic (0.10%), dihomo-γ-linolenic (DGLA, 2.96%) and arachidonic (10.72%) acids compared with the other ethnicities (all P ≤ 0.01). In contrast, Hispanics had the lowest mean levels of plasma EPA (0.70%) and DHA (3.49%), and the highest levels of DGLA (3.59%; all P ≤ 0.01). Significant differences in EPA and DHA among ethnicities were attenuated following adjustment for dietary non-fried fish and fish oil supplementation. Ethnicity did not modify the associations of LC-PUFAs with markers of inflammation or endothelial activation (all P (interaction)>0.05). CONCLUSIONS: The absence of a modifying effect of ethnicity indicates that the putative benefits of LC-PUFAs with respect to inflammation are pan-ethnic. Future longitudinal studies may elucidate the origin(s) of ethnicity-based differences in LC-PUFA composition and whether certain patterns, that is, high plasma levels of DGLA and low levels of EPA/DHA, contribute to inflammation-associated health outcomes.

Short- and long-term effects of nitrogen metabolism of feeding protein during mild or severe energy restriction.

The complex relationship between protein intake and energy restriction was studied in acutely and chronically restricted adult rats. Rats were fed either 12 or 24 kcal/day from protein alone or protein plus carbohydrate from 3 to 16 days in one experiment. In another, groups were fed either 0.75 or 1.5 g lactalbumin/day in diets supplying 90%, 80% or 70% of the ad libitum energy intake for 8 or 104 days. Body composition and nitrogen of various tissues were determined. In experiment 1, feeding protein conserved tissue and body nitrogen as long as sufficient adipose stores were maintained, but thereafter had no advantage over lower protein intakes supplemented with carbohydrate. In experiment 2, all rats gained weight in proportion to energy intake. Protein level was protective of carcass nitrogen, water and liver nitrogen in both the short- and long-term at the 80% and 90% level of energy intake. Energy intake was more important than protein in conserving muscle nitrogen. Effects of energy and protein restriction are complex and dependent upon the total amount of protein and energy provided, body reserves and duration of restriction.

Exchange of free cholesterol between low density lipoproteins and human adipocytes.

Free cholesterol uptake from low density lipoproteins (LDL) by fat cells was investigated using exchange-labelled [1,2-3H]cholesterol-LDL and isolated human adipocytes, prepared by collagenase digestion of subcutaneous fat tissue biopsies. Radioactivity appeared in the cellular lipids within 2 min and accumulated at a slower rate approaching linearity for 3 h. At 5 and 120 min, 90% of the recovered cellular radioactivity was found in the bulk lipid fraction and the remainder was distributed among organelle fractions. Uptake of [3H]cholesterol was linearly related to substrate concentrations up to 5 micrograms unesterified cholesterol - LDL . mL-1. At higher concentrations up to 22 micrograms unesterified cholesterol - LDL . mL-1, [1,2-3H]cholesterol accumulated more gradually but did not reach a plateau. Metabolic inhibitors, sodium azide plus sodium fluoride, had no effect on radiocholesterol uptake. Native LDL and high density lipoprotein at equivalent unesterified cholesterol concentrations decreased [1,2-3H]cholesterol uptake, to a similar extent suggesting isotope dilution. The results demonstrate a rapid, receptor-independent uptake of cholesterol from LDL by adipocytes, consistent with an exchange mechanism. This process could explain the rapid labelling of adipose tissue cholesterol in vivo following intravenous administration of radiocholesterol and efflux of free cholesterol from adipose tissue during starvation.