Effect of body fat distribution on the transcription response to dietary fat interventions

Combination of decreased energy expenditure and increased food intake results in fat accumulation either in the abdominal site (upper body obesity, UBO) or on the hips (lower body obesity, LBO). In this study, we used microarray gene expression profiling of adipose tissue biopsies to investigate the effect of body fat distribution on the physiological response to two dietary fat interventions. Mildly obese UBO and LBO male subjects (n = 12, waist-to-hip ratio range 0.93–1.12) were subjected to consumption of diets containing predominantly either long-chain fatty acids (PUFA) or medium-chain fatty acids (MCT). The results revealed (1) a large variation in transcription response to MCT and PUFA diets between UBO and LBO subjects, (2) higher sensitivity of UBO subjects to MCT/PUFA dietary intervention and (3) the upregulation of immune and apoptotic pathways and downregulation of metabolic pathways (oxidative, lipid, carbohydrate and amino acid metabolism) in UBO subjects when consuming MCT compared with PUFA diet. In conclusion, we report that despite the recommendation of MCT-based diet for improving obesity phenotype, this diet may have adverse effect on inflammatory and metabolic status of UBO subjects. The body fat distribution is, therefore, an important parameter to consider when providing personalized dietary recommendation

Short-term fatty acid intervention elicits differential gene expression responses in adipose tissue from lean and overweight men

The goal of this study was to investigate the effect of a short-term nutritional intervention on gene expression in adipose tissue from lean and overweight subjects. Gene expression profiles were measured after consumption of an intervention spread (increased levels of polyunsaturated fatty acids, conjugated linoleic acid and medium chain triglycerides) and a control spread (40 g of fat daily) for 9 days. Adipose tissue gene expression profiles of lean and overweight subjects were distinctly different, mainly with respect to defense response and metabolism. The intervention resulted in lower expression of genes related to energy metabolism in lean subjects, whereas expression of inflammatory genes was down-regulated and expression of lipid metabolism genes was up-regulated in the majority of overweight subjects. Individual responses in overweight subjects were variable and these correlated better to waist–hip ratio and fat percentage than BMI

Linking microarray reporters with protein functions

<p>Abstract</p> <p>Background</p> <p>The analysis of microarray experiments requires accurate and up-to-date functional annotation of the microarray reporters to optimize the interpretation of the biological processes involved. Pathway visualization tools are used to connect gene expression data with existing biological pathways by using specific database identifiers that link reporters with elements in the pathways.</p> <p>Results</p> <p>This paper proposes a novel method that aims to improve microarray reporter annotation by BLASTing the original reporter sequences against a species-specific EMBL subset, that was derived from and crosslinked back to the highly curated UniProt database. The resulting alignments were filtered using high quality alignment criteria and further compared with the outcome of a more traditional approach, where reporter sequences were BLASTed against EnsEMBL followed by locating the corresponding protein (UniProt) entry for the high quality hits. Combining the results of both methods resulted in successful annotation of > 58% of all reporter sequences with UniProt IDs on two commercial array platforms, increasing the amount of Incyte reporters that could be coupled to Gene Ontology terms from 32.7% to 58.3% and to a local GenMAPP pathway from 9.6% to 16.7%. For Agilent, 35.3% of the total reporters are now linked towards GO nodes and 7.1% on local pathways.</p> <p>Conclusion</p> <p>Our methods increased the annotation quality of microarray reporter sequences and allowed us to visualize more reporters using pathway visualization tools. Even in cases where the original reporter annotation showed the correct description the new identifiers often allowed improved pathway and Gene Ontology linking. These methods are freely available at http://www.bigcat.unimaas.nl/public/publications/Gaj_Annotation/.</p

A longitudinal study of gene expression in healthy individuals

<p>Abstract</p> <p>Background</p> <p>The use of gene expression in venous blood either as a pharmacodynamic marker in clinical trials of drugs or as a diagnostic test requires knowledge of the variability in expression over time in healthy volunteers. Here we defined a normal range of gene expression over 6 months in the blood of four cohorts of healthy men and women who were stratified by age (22–55 years and > 55 years) and gender.</p> <p>Methods</p> <p>Eleven immunomodulatory genes likely to play important roles in inflammatory conditions such as rheumatoid arthritis and infection in addition to four genes typically used as reference genes were examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), as well as the full genome as represented by Affymetrix HG U133 Plus 2.0 microarrays.</p> <p>Results</p> <p>Gene expression levels as assessed by qRT-PCR and microarray were relatively stable over time with ~2% of genes as measured by microarray showing intra-subject differences over time periods longer than one month. Fifteen genes varied by gender. The eleven genes examined by qRT-PCR remained within a limited dynamic range for all individuals. Specifically, for the seven most stably expressed genes (CXCL1, HMOX1, IL1RN, IL1B, IL6R, PTGS2, and TNF), 95% of all samples profiled fell within 1.5–2.5 Ct, the equivalent of a 4- to 6-fold dynamic range. Two subjects who experienced severe adverse events of cancer and anemia, had microarray gene expression profiles that were distinct from normal while subjects who experienced an infection had only slightly elevated levels of inflammatory markers.</p> <p>Conclusion</p> <p>This study defines the range and variability of gene expression in healthy men and women over a six-month period. These parameters can be used to estimate the number of subjects needed to observe significant differences from normal gene expression in clinical studies. A set of genes that varied by gender was also identified as were a set of genes with elevated expression in a subject with iron deficiency anemia and another subject being treated for lung cancer.</p

Differential transcriptomic profiles effected by oil palm phenolics indicate novel health outcomes

Abstract Background Plant phenolics are important nutritional antioxidants which could aid in overcoming chronic diseases such as cardiovascular disease and cancer, two leading causes of death in the world. The oil palm (Elaeis guineensis) is a rich source of water-soluble phenolics which have high antioxidant activities. This study aimed to identify the in vivo effects and molecular mechanisms involved in the biological activities of oil palm phenolics (OPP) during healthy states via microarray gene expression profiling, using mice supplemented with a normal diet as biological models. Results Having confirmed via histology, haematology and clinical biochemistry analyses that OPP is not toxic to mice, we further explored the gene expression changes caused by OPP through statistical and functional analyses using Illumina microarrays. OPP showed numerous biological activities in three major organs of mice, the liver, spleen and heart. In livers of mice given OPP, four lipid catabolism genes were up-regulated while five cholesterol biosynthesis genes were down-regulated, suggesting that OPP may play a role in reducing cardiovascular disease. OPP also up-regulated eighteen blood coagulation genes in spleens of mice. OPP elicited gene expression changes similar to the effects of caloric restriction in the hearts of mice supplemented with OPP. Microarray gene expression fold changes for six target genes in the three major organs tested were validated with real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and the correlation of fold changes obtained with these two techniques was high (R2 = 0.9653). Conclusions OPP showed non-toxicity and various pleiotropic effects in mice. This study implies the potential application of OPP as a valuable source of wellness nutraceuticals, and further suggests the molecular mechanisms as to how dietary phenolics work in vivo.</p

Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns

Nutrigenetics and Nutrigenomics: Viewpoints on the Current Status and Applications in Nutrition Research and Practice

Nutrigenetics and nutrigenomics hold much promise for providing better nutritional advice to the public generally, genetic subgroups and individuals. Because nutrigenetics and nutrigenomics require a deep understanding of nutrition, genetics and biochemistry and ever new ‘omic’ technologies, it is often difficult, even for educated professionals, to appreciate their relevance to the practice of preventive approaches for optimising health, delaying onset of disease and diminishing its severity. This review discusses (i) the basic concepts, technical terms and technology involved in nutrigenetics and nutrigenomics; (ii) how this emerging knowledge can be applied to optimise health, prevent and treat diseases; (iii) how to read, understand and interpret nutrigenetic and nutrigenomic research results, and (iv) how this knowledge may potentially transform nutrition and dietetic practice, and the implications of such a transformation. This is in effect an up-to-date overview of the various aspects of nutrigenetics and nutrigenomics relevant to health practitioners who are seeking a better understanding of this new frontier in nutrition research and its potential application to dietetic practice