Journal of Nutrigenetics and Nutrigenomics最新文献

MicroRNAs (miRNAs) are a class of evolutionarily conserved, small non-coding RNAs of 19-24 nucleotides in length that regulate gene expression mostly at the posttranscriptional level. They are known to be involved in the control of different processes such as cell cycling, programmed cell death, cell differentiation, tumor development, metastasis, and sensing of nutrient stress. This review summarizes the evidence regarding the changes in miRNA expression that are caused by diets with a deficiency or augmented intake of nutrients such as amino acids, carbohydrates, fatty acids, vitamins, and phytochemicals. As diet is known to influence the expression of miRNAs, miRNA profiling has the potential to be useful in the assessment of nutritional status in dietary intervention studies. Additionally, as it can change miRNA expression, diet may be used as a therapeutic agent to treat many different diseases. Also, we explored here some ideas on therapeutics based on the manipulation of miRNA expression levels for dietary-derived diseases as well as the putative effect of food-derived miRNAs on host gene expression.

Background/aims: Saturated fatty acids (SFA) are widely thought to induce inflammation in adipose tissue (AT), while monounsaturated fatty acids (MUFA) are purported to have the opposite effect; however, it is unclear if individual SFA and MUFA behave similarly. Our goal was to examine adipocyte transcriptional networks regulated by individual SFA (palmitic acid, PA; stearic acid, SA) and MUFA (palmitoleic acid, PMA; oleic acid, OA).

Methods: Differentiated preadipocytes were treated with either 250 µM PA, SA, PMA, or OA for 48 h. Gene expression was analyzed using microarrays and real-time RT-PCR. Data were compared with those of a previous study reporting AT gene expression in humans following the consumption of SFA- or MUFA-enriched diets.

Results: Individual fatty acid treatments had significant effects on adipocyte gene expression. Functional analyses revealed that PA induced the TLR signalling pathway, while PMA had the opposite effect. SA and OA had similar effects, with increases in key metabolic pathways including mTOR and PPAR signalling and a reduction in TLR signalling. Ccl5 was validated as a candidate gene that may mediate the differential inflammatory effects of SFA and MUFA in AT.

Conclusions: Individual SFA and MUFA trigger distinct transcriptional responses in differentiated preadipocytes, with inflammatory and metabolic pathways particularly sensitive to these fatty acids.

Background/aims: Transcriptomics technology in human nutrition intervention studies would allow for genome-wide screening of the effects of nutrients. We observed the time course of gene expression changes in peripheral white blood cells (WBC) to elucidate the metabolic changes in the postprandial state that are a reflection and a marker of whole body metabolic changes.

Methods: In a randomized crossover study, 7 healthy subjects consumed test meals of glucose (GL), white rice (WR) and rolled barley (BAR), each containing 75 g of available carbohydrate, and water (WAT). Blood glucose, insulin and nonesterified fatty acid concentrations, as well as the subjective levels of fullness and hunger were measured. Microarray analysis of the WBC and the real-time PCR were examined during 360 min after the intake of the test meals.

Results: The number of genes that changed more than 1.5-fold and the expression patterns in the time course were different between the GL, the WR and the BAR groups. Several genes involved in glycolysis and fatty acid β-oxidation were markedly changed after the intake of the GL, the WR and the BAR; however, these genes did not change at any time point in the WAT.

Conclusions: Gene expression profiling in the WBC can reflect food-related metabolic changes, even in the postprandial state.

Background/aims: Vitamin D regulates gene transcription by binding to the vitamin D receptor (VDR), potentially affecting cardiometabolic disease risk. However, studies of 25-hydroxyvitamin D [25(OH)D] and cardiometabolic disease are inconsistent. Inconsistencies may result from unaccounted for interactions between VDR genetic variants and 25(OH)D. We examined the effect of 25(OH)D on the association between VDR variants and cardiometabolic disease biomarkers.

Methods: The relationship between 25(OH)D, 24 VDR variants, and 10 cardiometabolic biomarkers was examined in 488 Caucasians aged 20-29 years. Covariate-adjusted general linear models were used to examine the interaction effect of 25(OH)D × VDR on each biomarker. When interactions were significant (p < 0.05), relationships were further examined with analysis of covariance, stratified by tertiles of 25(OH)D and adjusted for multiple comparisons.

Results: In the lowest tertile of 25(OH)D, major allele homozygotes for rs3819545 had higher insulin and HOMA-IR than minor allele carriers (p ≤ 0.002). Fasting insulin and HOMA-IR were lower in the highest than the lowest tertile of 25(OH)D among major allele homozygotes (p < 0.0001), but minor allele carriers had similar levels regardless of vitamin D status.

Conclusions: We identified 25(OH)D-dependent associations between rs3819545 and glycemic dysregulation biomarkers. Major allele homozygotes with low vitamin D status may be at increased risk of insulin resistance.

Epigenetic mechanisms are likely to play an important role in the regulation of metabolism and body weight through gene-nutrient interactions. This review focuses on methods for analyzing one of the most important epigenetic mechanisms, DNA methylation, from single nucleotide to global measurement depending on the study goal and scope. In addition, this study highlights the major principles and methods for DNA methylation analysis with emphasis on nutritional applications. Recent developments concerning epigenetic technologies are showing promising results of DNA methylation levels at a single-base resolution and provide the ability to differentiate between 5-methylcytosine and other nucleotide modifications such as 5-hydroxymethylcytosine. A large number of methods can be used for the analysis of DNA methylation such as pyrosequencing™, primer extension or real-time PCR methods, and genome-wide DNA methylation profile from microarray or sequencing-based methods. Researchers should conduct a preliminary analysis focused on the type of validation and information provided by each technique in order to select the best method fitting for their nutritional research interests.

Background/aims: The common polymorphism in the FTO gene (rs9939609) has been associated with obesity, type 2 diabetes, and appetite regulation. The aim of this study was to evaluate possible associations of FTO rs9939609 with dietary factors in patients with type 2 diabetes.

Methods: This was a cross-sectional study of 236 patients with type 2 diabetes (age 60.0 ± 10.3 years; diabetes duration 12.7 ± 8.2 years; 53.4% females) who were genotyped for FTO rs9939609. Patients underwent clinical and laboratory evaluations and 3-day weighed diet records. Data on dietary intake were categorized as high or low, based on median values.

Results: The AA genotype in the FTO gene was positively associated with high fat (>34% energy; OR = 2.17; 95% CI 1.02-4.63) and low fiber intakes (<16 g/day; OR = 2.42; 95% CI 1.05-5.57), adjusted for gender, BMI, total energy intake, systolic blood pressure, and HbA1c. When gender was taken into account, AA females had higher fat (37.4 ± 5.3 vs. 32.6 ± 7.5 and 32.2 ± 6.2% energy; p = 0.005) and lower fiber intakes (12.4 ± 4.4 vs. 15.1 ± 6.3 and 16.7 ± 5.6 g/day; p = 0.023) than patients with TT and AT genotypes. Multiple logistic regression models confirmed female associations for high fat (OR = 9.73; 95% CI 2.12-44.66) and low fiber intakes (OR = 4.28; 95% CI 1.14-16.06; p < 0.05 for all models).

Conclusions: Patients with type 2 diabetes, who were carriers of the AA genotype of the FTO rs9939609, had increased fat and decreased fiber consumption, independently of BMI.

Background/aims: Chemicals that interfere with reactive oxygen species metabolism can act as potential candidates for the treatment of cancer. Some of the glucosides of citrus limonin inhibit the endogenously generated reactive oxygen species. The aim is to study the interactions of limonin with chemotherapy.

Methods: Breast cancer cell lines MCF-7 (p53 wild type) and MDA-MB-231 (p53 mutant) as well as the nontumorigenic epithelial cell line MCF-10 were used to screen the effect of limonin at 1-, 5- and 10-µM concentrations with camptothecin for apoptosis and NFĸB, p38 and ERK-MAPK signaling kinase assays. The effect of cyclophosphamide and limonin on MDA MB 231 xenografts was also studied.

Results: Our results indicate that limonin did not inhibit camptothecin-induced apoptosis in human breast cancer cells in vitro through noninterference of camptothecin-induced phosphorylation of p38 MAPK and ERK-MAPK. Using an in vivo model of human breast cancer, limonin in combination with cyclophosphamide was not found to inhibit the cyclophosphamide-induced tumor regression through a reduced mitotic index of tumor xenograft cells when compared to treatment with cyclophosphamide alone.

Conclusion: Both in vitro and in vivo results suggest that limonin could be beneficial for breast cancer patients undergoing chemotherapy.

Background/aims: We studied peroxisome proliferator-activated receptor-γ coactivator-1α (PPARGC1A) gene variations at the 23815227-23815706 positions and examined their possible correlation with obesity-related conditions and resting energy expenditure (REE). We investigated the expression of PPARGC1A, mitogen-activated protein kinase (MAPK) and uncoupling protein 2 (UCP2), which play key roles in cellular energy expenditure, in a cellular model consisting of peripheral blood mononuclear cells, and compared them with various genotypes of the PPARGC1A gene.

Methods: In total, 100 normal-weight and 129 obese subjects participated in the current study. All subjects were assessed for REE and body composition. We sequenced the PPARGC1A gene. Real-time PCR was used for determining the PPARGC1A, MAPK, and UCP2 gene expression.

Results: There were significant differences in terms of body mass index, fat mass, low-density lipoprotein, insulin levels, REE/kg body weight, and REE/lean body mass among rs17574213 genotypes. There were significant differences in total cholesterol and low-density lipoprotein cholesterol levels among the various genotypes of Gly482Ser (rs8192678) and rs3755863. The relative PPARGC1A, MAPK, and UCP2 gene expressions had similar trends in the two studied SNPs, and the expression level of these genes was lowest in the TT genotype of Gly482Ser and rs3755863 and highest in the CC genotype of Gly482Ser and rs3755863.

Conclusions: Our findings suggest that PPARGC1A variations may influence PPARGC1A expression and the coordinating regulators of downstream targets in energy homeostasis. Further study is needed to shed some light on this process.