Eileen R. Gibney

Epigenetics and gene expression

Transcription, translation and subsequent protein modification represent the transfer of genetic information from the archival copy of DNA to the short-lived messenger RNA, usually with subsequent production of protein. Although all cells in an organism contain essentially the same DNA, cell types and functions differ because of qualitative and quantitative differences in their gene expression. Thus, control of gene expression is at the heart of differentiation and development. Epigenetic processes, including DNA methylation, histone modification and various RNA-mediated processes, are thought to influence gene expression chiefly at the level of transcription; however, other steps in the process (for example, translation) may also be regulated epigenetically. The following paper will outline the role epigenetics is believed to have in influencing gene expression.

Folic acid levels in some food staples in Ireland are on the decline: implications for passive folic acid intakes?

BACKGROUND Neural tube defects are largely preventable by the maternal periconceptual consumption of folic acid. The aim of this study was to examine the levels of synthetic folic acid in foods and the range of food stuffs with added folic acid available to consumers in Ireland at the current time. METHODS Three audits of fortified foods available in supermarkets in the Republic of Ireland were conducted. Researchers visited supermarkets and obtained folic acid levels from nutrition labels in 2004, 2008 and 2013/4. Levels were compared using MS Excel. RESULTS The profile of foods fortified with folic acid in 2013/4 has changed since 2004. The percentage of foods fortified with folic acid has decreased as has the level of added folic acid in some food staples, such as fat/dairy spreads. CONCLUSION Bread, milk and spreads no longer contain as much folic acid as previously (2004 and 2008). This may contribute to a decrease in folate intake and therefore may contribute to an increase in NTD rates. Research on current blood concentrations of folate status markers is now warranted.

Online Dietary Intake Estimation: Reproducibility and Validity of the Food4Me Food Frequency Questionnaire Against a 4-Day Weighed Food Record

Background Advances in nutritional assessment are continuing to embrace developments in computer technology. The online Food4Me food frequency questionnaire (FFQ) was created as an electronic system for the collection of nutrient intake data. To ensure its accuracy in assessing both nutrient and food group intake, further validation against data obtained using a reliable, but independent, instrument and assessment of its reproducibility are required. Objective The aim was to assess the reproducibility and validity of the Food4Me FFQ against a 4-day weighed food record (WFR). Methods Reproducibility of the Food4Me FFQ was assessed using test-retest methodology by asking participants to complete the FFQ on 2 occasions 4 weeks apart. To assess the validity of the Food4Me FFQ against the 4-day WFR, half the participants were also asked to complete a 4-day WFR 1 week after the first administration of the Food4Me FFQ. Level of agreement between nutrient and food group intakes estimated by the repeated Food4Me FFQ and the Food4Me FFQ and 4-day WFR were evaluated using Bland-Altman methodology and classification into quartiles of daily intake. Crude unadjusted correlation coefficients were also calculated for nutrient and food group intakes. Results In total, 100 people participated in the assessment of reproducibility (mean age 32, SD 12 years), and 49 of these (mean age 27, SD 8 years) also took part in the assessment of validity. Crude unadjusted correlations for repeated Food4Me FFQ ranged from .65 (vitamin D) to .90 (alcohol). The mean cross-classification into “exact agreement plus adjacent” was 92% for both nutrient and food group intakes, and Bland-Altman plots showed good agreement for energy-adjusted macronutrient intakes. Agreement between the Food4Me FFQ and 4-day WFR varied, with crude unadjusted correlations ranging from .23 (vitamin D) to .65 (protein, % total energy) for nutrient intakes and .11 (soups, sauces and miscellaneous foods) to .73 (yogurts) for food group intake. The mean cross-classification into “exact agreement plus adjacent” was 80% and 78% for nutrient and food group intake, respectively. There were no significant differences between energy intakes estimated using the Food4Me FFQ and 4-day WFR, and Bland-Altman plots showed good agreement for both energy and energy-controlled nutrient intakes. Conclusions The results demonstrate that the online Food4Me FFQ is reproducible for assessing nutrient and food group intake and has moderate agreement with the 4-day WFR for assessing energy and energy-adjusted nutrient intakes. The Food4Me FFQ is a suitable online tool for assessing dietary intake in healthy adults.

Enhancing cognitive functioning in the elderly: multicomponent vs resistance training

Purpose The primary purpose of this study was to compare the effects of two different exercise training programs on executive cognitive functions and functional mobility in older adults. A secondary purpose was to explore the potential mediators of training effects on executive function and functional mobility with particular reference to physical fitness gains. Methods A sample of 42 healthy community dwelling adults aged 65 to 75 years participated twice weekly for 3 months in either: (1) multicomponent training, prioritizing neuromuscular coordination, balance, agility, and cognitive executive control; or (2) progressive resistance training for strength conditioning. Participants were tested at baseline (T1), following a 4-week control period (T2), and finally at postintervention (T3) for executive function (inhibition and cognitive flexibility) and functional mobility (maximal walking speed with and without additional task requirements). Cardiorespiratory and muscular fitness were also assessed as potential mediators. Results Indices of inhibition, the functions involved in the deliberate withholding of prepotent or automatic responses, and measures of functional mobility improved after the intervention, independent of training type. Mediation analysis suggested that different mechanisms underlie the effects of multicomponent and progressive resistance training. While multicomponent training seemed to directly affect inhibitory capacity, resistance training seemed to affect it indirectly through gains in muscular strength. Physical fitness and executive function variables did not mediate functional mobility changes. Conclusion These results confirm that physical training benefits executive function and suggest that different training types might lead to such benefits through different pathways. Both types of training also promoted functional mobility in older adulthood; however, neither inhibitory capacity, nor muscular strength gains seemed to explain functional mobility outcomes.

Online dietary intake estimation: The Food4Me food frequency questionnaire

Background Dietary assessment methods are important tools for nutrition research. Online dietary assessment tools have the potential to become invaluable methods of assessing dietary intake because, compared with traditional methods, they have many advantages including the automatic storage of input data and the immediate generation of nutritional outputs. Objective The aim of this study was to develop an online food frequency questionnaire (FFQ) for dietary data collection in the “Food4Me” study and to compare this with the validated European Prospective Investigation of Cancer (EPIC) Norfolk printed FFQ. Methods The Food4Me FFQ used in this analysis was developed to consist of 157 food items. Standardized color photographs were incorporated in the development of the Food4Me FFQ to facilitate accurate quantification of the portion size of each food item. Participants were recruited in two centers (Dublin, Ireland and Reading, United Kingdom) and each received the online Food4Me FFQ and the printed EPIC-Norfolk FFQ in random order. Participants completed the Food4Me FFQ online and, for most food items, participants were requested to choose their usual serving size among seven possibilities from a range of portion size pictures. The level of agreement between the two methods was evaluated for both nutrient and food group intakes using the Bland and Altman method and classification into quartiles of daily intake. Correlations were calculated for nutrient and food group intakes. Results A total of 113 participants were recruited with a mean age of 30 (SD 10) years (40.7% male, 46/113; 59.3%, 67/113 female). Cross-classification into exact plus adjacent quartiles ranged from 77% to 97% at the nutrient level and 77% to 99% at the food group level. Agreement at the nutrient level was highest for alcohol (97%) and lowest for percent energy from polyunsaturated fatty acids (77%). Crude unadjusted correlations for nutrients ranged between .43 and .86. Agreement at the food group level was highest for “other fruits” (eg, apples, pears, oranges) and lowest for “cakes, pastries, and buns”. For food groups, correlations ranged between .41 and .90. Conclusions The results demonstrate that the online Food4Me FFQ has good agreement with the validated printed EPIC-Norfolk FFQ for assessing both nutrient and food group intakes, rendering it a useful tool for ranking individuals based on nutrient and food group intakes.

The 19-bp deletion polymorphism in intron-1 of dihydrofolate reductase (DHFR) may decrease rather than increase risk for spina bifida in the irish population

Periconceptional maternal folic acid supplementation can prevent up to 70% of pregnancies affected with neural tube defects (NTDs), including spina bifida. This has focused attention on folate‐related genes such as dihydrofolate reductase (DHFR) in a bid to identify the genetic factors that influence NTD risk through either the fetal or maternal genotype. We considered a novel intronic 19‐bp deletion polymorphism and two polymorphisms within the 3′ untranslated region (721A > T and 829C > T) of the DHFR gene as candidates for NTD risk. We studied NTD cases (n = 283), mothers of cases (n = 280), fathers of cases (n = 279), and controls (n = 256). We did not find the DHFR 829C > T polymorphism to be variable within the Irish population. The 19‐bp intron deletion and the 721A > T polymorphisms were found to be in linkage disequilibrium. In contrast to a previous study, the 19‐bp intron deletion allele did show a significant protective effect in mothers of NTD cases when present in one (relative risk 0.59 [95%CI: 0.39–0.89], P = 0.01) or two copies (relative risk 0.52 [95%CI: 0.32–0.86], P = 0.01). Analysis of mRNA levels revealed a small increase in expression (∼1.5‐fold) associated with the 19‐bp intron deletion polymorphism, but this was not significant. In conclusion, the DHFR intron 19‐bp deletion allele may be a protective NTD genetic factor by increasing DHFR mRNA levels in pregnant women.

Total energy expenditure in patients with small-cell lung cancer: results of a validated study using the bicarbonate-urea method.

The bicarbonate-urea method for measuring CO2 production was applied to eight free-living patients (mean age, 68 +/- 10 years; mean weight, 69 +/- 10 kg; mean height, 1.65 +/- 0.10 m) with unresectable small-cell lung cancer for a period of 1 day (n = 5) or 2 days (n = 3). The basal metabolic rate (BMR) was measured in all subjects. The technique was first validated against whole-body indirect calorimetry over an additional 24-hour period in five of these subjects. The bicarbonate-urea method predicted net CO2 production to be 102.1% +/- 3.4% of that measured by whole-body indirect calorimetry, and energy expenditure, 101.5% +/- 3.8% of the measured calorimeter value (8.1 +/- 1.6 MJ/d). The 24-hour recovery of label in CO2 excreted by the body was 95.6% +/- 0.5%. In free-living conditions, the bicarbonate-urea method predicted energy expenditure to be 9.0 +/- 2.6 MJ/d. BMR was elevated by a mean of 6% (P < .05) compared with the Schofield standards. The physical activity level ([PAL] the ratio of total energy expenditure [TEE] to BMR) was variable (1.15 to 1.87), but the mean value was only 1.36 +/- 0.22, considerably less than that of moderately active healthy subjects with estimated PAL values of 1.55 (P < .05) to 1.65 (P < .01) and the mean results obtained by doubly labeled water (previous studies) in healthy age- and sex-matched subjects. This is the first time a tracer method for measuring CO2 production and energy expenditure has been validated against whole-body 24-hour indirect calorimetry in patients with lung cancer or a systemic inflammatory reaction. The agreement between the two methods is similar to that observed in normal subjects. This is also the first time a tracer method has been used to measure energy expenditure in free-living patients with lung cancer. The results suggest that TEE and the energy requirements necessary to maintain energy balance were not increased despite basal hypermetabolism, because of the associated decrease in physical activity.

Plasma concentrations of alpha-MSH, AgRP and leptin in lean and obese men and their relationship to differing states of energy balance perturbation

objective  A great deal of attention has focused on the central role of alpha melanocyte‐stimulating hormone (α‐MSH) and its antagonism at the melanocortin‐4 receptor (MC4R) by agouti related protein (AgRP) in the regulation of energy balance. However, very little is known regarding the function of circulating AgRP and α‐MSH in humans. We aimed to determine whether circulating α‐MSH and AgRP are responsive to long‐term perturbations in energy balance, in a manner consistent with their central putative functions.

Epigenetic regulation in obesity.

Purpose of reviewResearch suggests that 65% of variation in obesity is genetic. However, much of the known genetic associations have little known function and their effect size small, thus the gene–environment interaction, including epigenetic influences on gene expression, is suggested to be an important factor in the susceptibilty to obesity. This review will explore the potential of epigenetic markers to influence expression of genes associated with obesity. Recent findingsEpigenetic changes in utero are known to have direct implications on the phenotype of the offspring. More recently work has focused on how such epigenetic changes continue to regulate risk of obesity from infancy through to adulthood. Work has shown that, for example, hypomethylation of the MC4 gene causes an increase in expression, and has a direct impact on appetite and intake, and thus influences risk of obesity. Similar influences are also seen in other aspects of obesity including inflammation and adiposity. SummaryMaternal diet during foetal development has many epigenetic implications, which affect the offsprings risk factors for obesity during childhood and adulthood, and even in subsequent generations. Genes associated with risk of obesity, are susceptible to epigenetic mutations, which have subsequent effects on disease mechanisms, such as appetite and impaired glucose and insulin tolerance.

The relationship between BMI and metabolomic profiles: a focus on amino acids

The role of metabolomics in the field of nutrition is continuing to grow and it has the potential to assist in the understanding of metabolic regulation and explain how minor perturbations can have a multitude of biochemical endpoints. It is this development, which creates the potential to provide the knowledge necessary to facilitate a more targeted approach to nutrition. In recent years, there has been interest in applying metabolomics to examine alterations in the metabolic profile according to weight gain/obesity. Emerging from these studies is the strong evidence that alterations in the amino acid (AA) profiles are associated with obesity. Several other studies have also shown a relationship between branched-chain amino acids (BCAA), obesity and insulin resistance. The present review focuses on the proposed link between AA and in particular BCAA, obesity and insulin resistance. In conclusion, a wealth of information is accumulating to support the role of AA, and in particular of the BCAA, in obesity.