Genes & Nutrition最新文献

Background: Increased adipogenesis and altered adipocyte function contribute to the development of obesity and associated comorbidities. Fructose modified adipocyte metabolism compared to glucose, but the regulatory mechanisms and consequences for obesity are unknown. Genome-wide methylation and global transcriptomics in SGBS pre-adipocytes exposed to 0, 2.5, 5, and 10 mM fructose, added to a 5-mM glucose-containing medium, were analyzed at 0, 24, 48, 96, 192, and 384 h following the induction of adipogenesis.

Results: Time-dependent changes in DNA methylation compared to baseline (0 h) occurred during the final maturation of adipocytes, between 192 and 384 h. Larger percentages (0.1% at 192 h, 3.2% at 384 h) of differentially methylated regions (DMRs) were found in adipocytes differentiated in the glucose-containing control media compared to adipocytes differentiated in fructose-supplemented media (0.0006% for 10 mM, 0.001% for 5 mM, and 0.005% for 2.5 mM at 384 h). A total of 1437 DMRs were identified in 5237 differentially expressed genes at 384 h post-induction in glucose-containing (5 mM) control media. The majority of them inversely correlated with the gene expression, but 666 regions were positively correlated to the gene expression.

Conclusions: Our studies demonstrate that DNA methylation regulates or marks the transformation of morphologically differentiating adipocytes (seen at 192 h), to the more mature and metabolically robust adipocytes (as seen at 384 h) in a genome-wide manner. Lower (2.5 mM) concentrations of fructose have the most robust effects on methylation compared to higher concentrations (5 and 10 mM), suggesting that fructose may be playing a signaling/regulatory role at lower concentrations of fructose and as a substrate at higher concentrations.

Objective: This study aimed to quantitatively summarize the evidence for VDR BsmI gene polymorphism and osteoporosis risk in postmenopausal women.

Materials and methods: The PubMed, EMBASE, Weipu, CNKI, and Wanfang databases were searched for eligible studies. Case-control studies containing available genotype frequencies of B/b were chosen, and odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of this association.

Results: 4485 osteoporosis and 5490 controls were identified in our meta-analysis. In the stratified analysis, a significant association was observed between VDR BsmI gene polymorphism and osteoporosis susceptibility in Caucasians (additive model: OR = 0.809, 95% CI 0.678~0.965, p = 0.019; recessive model: OR = 0.736, 95% CI 0.568~0.955, p = 0.021; and co-dominant model: bb vs. BB OR = 0.701, 95% CI 0.511~0.962 p = 0.028), and we failed to find any significant relationship in Asians.

Conclusion: The present meta-analysis suggests that VDR BsmI genotype is associated with increased risk of postmenopausal osteoporosis in Caucasians but not in Asians. To draw comprehensive and true conclusions, further prospective studies with larger numbers of participants worldwide are needed to examine associations between VDR BsmI polymorphism and osteoporosis in postmenopausal women.

Background: Cardiometabolic diseases are complex traits which are influenced by several single nucleotide polymorphisms (SNPs). Thus, analysing the combined effects of multiple gene variants might provide a better understanding of disease risk than using a single gene variant approach. Furthermore, studies have found that the effect of SNPs on cardiometabolic traits can be influenced by lifestyle factors, highlighting the importance of analysing gene-lifestyle interactions.

Aims: In the present study, we investigated the association of 15 gene variants with cardiometabolic traits and examined whether these associations were modified by lifestyle factors such as dietary intake and physical activity.

Methods: The study included 110 Minangkabau women [aged 25-60 years and body mass index (BMI) 25.13 ± 4.2 kg/m²] from Padang, Indonesia. All participants underwent a physical examination followed by anthropometric, biochemical and dietary assessments and genetic tests. A genetic risk score (GRS) was developed based on 15 cardiometabolic disease-related SNPs. The effect of GRS on cardiometabolic traits was analysed using general linear models. GRS-lifestyle interactions on continuous outcomes were tested by including the interaction term (e.g. lifestyle factor*GRS) in the regression model. Models were adjusted for age, BMI and location (rural or urban), wherever appropriate.

Results: There was a significant association between GRS and BMI, where individuals carrying 6 or more risk alleles had higher BMI compared to those carrying 5 or less risk alleles (P = 0.018). Furthermore, there were significant interactions of GRS with protein intake on waist circumference (WC) and triglyceride concentrations (P_interaction = 0.002 and 0.003, respectively). Among women who had a lower protein intake (13.51 ± 1.18% of the total daily energy intake), carriers of six or more risk alleles had significantly lower WC and triglyceride concentrations compared with carriers of five or less risk alleles (P = 0.0118 and 0.002, respectively).

Conclusions: Our study confirmed the association of GRS with higher BMI and further showed a significant effect of the GRS on WC and triglyceride levels through the influence of a low-protein diet. These findings suggest that following a lower protein diet, particularly in genetically predisposed individuals, might be an effective approach for addressing cardiometabolic diseases among Southeast Asian women.

Background: This study evaluated gene-nutrition interactions between folate and the aberrant DNA methylation of tumor suppressor genes in different stages of carcinogenesis of esophageal squamous cell carcinoma (ESCC).

Methods: Two hundred ESCC cases, 200 esophageal precancerous lesion (EPL) cases, and 200 controls matched by age (± 2 years) and gender were used for this study. Baseline data and dietary intake information was collected via questionnaire. The serum folate levels and methylation status of promoter regions of p16 and p53 were detected.

Results: The interactions of increased serum folate level with unmethylated p16 and p53 promoter regions were significantly associated with a reduced risk of both EPL and ESCC (p for interaction < 0.05). The interactions of the lowest quartile of serum folate level with p16 or p53 methylation was significantly associated with an increased risk of ESCC (OR = 2.96, 95% CI, 1.45-6.05; OR = 2.34, 95% CI, 1.15-4.75). An increased serum folate level was also related to a decreasing trend of EPL and ESCC risks when p16 or p53 methylation occurred. The interaction of spinach, Chinese cabbage, liver and bean intake with unmethylated p16 and p53 was significantly associated with a reduced risk of EPL or ESCC (p for interaction < 0.05).

Conclusions: The interactions between a high folate level and unmethylated p16 and p53 promoter regions may have a strong preventive effect on esophageal carcinogenesis. Additionally, a high folate level may offset the tumor-promoting effects of aberrant DNA methylation of the genes, but it is also noteworthy that a very high level of folate may not have a protective effect on EPL in some cases.

Grapes and berries are two types of widely consumed fruits characterized by a high content in different phytochemicals. However, their accurate dietary assessment is particularly arduous, because of the already wide recognized bias associated with self-reporting methods, combined with the large range of species and cultivars and the fact that these fruits are popularly consumed not only in fresh and frozen forms but also as processed and derived products, including dried and canned fruits, beverages, jams, and jellies. Reporting precise type and/or quantity of grape and berries in FFQ or diaries can obviously be affected by errors. Recently, biomarkers of food intake (BFIs) rose as a promising tool to provide accurate information indicating consumption of certain food items. Protocols for performing systematic reviews in this field, as well as for assessing the validity of candidate BFIs have been developed within the Food Biomarker Alliance (FoodBAll) Project. This paper aims to evaluate the putative BIFs for blueberries, strawberries, raspberries, blackberries, cranberries, blackcurrant, and grapes. Candidate BFIs for grapes were resveratrol metabolites and tartaric acid. The metabolites considered as putative BFI for berries consumption were mostly anthocyanins derivatives together with several metabolites of ellagitannins and some aroma compounds. However, identification of BFIs for single berry types encountered more difficulties. In the absence of highly specific metabolites reported to date, we suggested some multi-metabolite panels that may be further investigated as putative biomarkers for some berry fruits.

Background: Nutrigenomics is an emerging science that studies the relationship between genes, diet and nutrients that can help prevent chronic disease. The development of this science depends on whether the public accept its application; therefore, predicting their intention to adopt it is important for its successful implementation.

Objective: This study aims to analyse Malaysian stakeholders' intentions to adopt nutrigenomics, and determines the factors that influence their intentions.

Methods: A survey was conducted based on the responses of 421 adults (aged 18 years and older) and comprising two stakeholder groups: healthcare providers (n = 221) and patients (n = 200) who were located in the Klang Valley, Malaysia. The SPSS software was used to analyse the descriptive statistics of intention to adopt nutrigenomics and the SmartPLS software was used to determine the predicting factors affecting their decisions to adopt nutrigenomics.

Results: The results show that the stakeholders perceived the benefits of nutrigenomics as outweighing its risks, suggesting that the perceived benefits represent the most important direct predictor of the intention to adopt nutrigenomics. The perceived risks of nutrigenomics, trust in key players, engagement with medical genetics and religiosity also predict the intention to adopt nutrigenomics. Additionally, the perceived benefits of nutrigenomics served as a mediator for four factors: perceived risks of nutrigenomics, engagement with medical genetics, trust in key players and religiosity, whilst the perceived risks were a mediator for engagement with medical genetics.

Conclusion: The findings of this study suggest that the intentions of Malaysian stakeholders to adopt nutrigenomics are a complex decision-making process where all the previously mentioned factors interact. Although the results showed that the stakeholders in Malaysia were highly positive towards nutrigenomics, they were also cautious about adopting it.

Background: Obesity is characterized by low-grade chronic inflammation and an excess of adipose tissue. The ASC gene encodes a protein that is part of the NLRP3 inflammasome, a cytosolic multiprotein complex that is associated with inflammation and metabolic alterations. To our knowledge, there is no evidence regarding ASC gene activity in obese adults in response to lifestyle modifications.

Purpose: To evaluate the effect of hypocaloric diet and moderate-intensity structured exercise intervention on ASC gene expression and inflammatory markers in obese adults.

Methods: Thirty-seven obese individuals aged 25 to 50 years were randomized to the hypocaloric diet exercise group or hypocaloric diet group. The participants underwent a 4-month follow-up. Electrical bioimpedance was used for body composition analysis. Biochemical data were analyzed by dry chemistry and insulin levels by ELISA. ASC gene expression from peripheral blood was performed using real-time PCR. Dietary data was collected through questionnaires and analyzed using the Nutritionist Pro™ software. Quantification of cytokines was conducted using Bio-Plex Pro™ Human cytokine. The Astrand-Ryhming test was used to estimate the maximum oxygen volume and design the moderate-intensity structured exercise program ~ 75% heart rate (HR) RESULTS: After the intervention, both study groups significantly improved body composition (decreased weight, fat mass, waist circumference and abdominal obesity, p < 0.05). Besides, the diet-exercise group significantly decreased ASC mRNA expression, MCP-1, and MIP-1β inflammatory cytokines compared to the diet group (p < 0.05). While in the diet group, MCP-1 and IL-8 exhibited significantly decreased levels (p < 0.05). In the diet-exercise group, a positive correlation between the atherogenic index and waist circumference was found (r = 0.822, p = 0.011), and a negative correlation was observed between the delta of ASC mRNA expression and IL-10 levels at the end of the intervention (r = - 0.627, p = 0.019).

Conclusion: Low-grade chronic inflammation was attenuated through individualized exercise prescription and our findings highlight the role of the ASC gene in the inflammation of obese adults.

Trial registration: ClinicalTrials.gov , number NCT04315376 . Registered 20 March 2020-retrospectively registered.

Background: Testosterone deficiency in men is clinically associated with the development of metabolic syndrome, which manifests as obesity, hepatic steatosis, and type-2 diabetes. We investigated the effects of castration-induced testosterone deficiency on body adiposity and the expression of genes related to lipid metabolism and glucose uptake and androgen signaling in male rats fed a normal diet (ND) or a high-fat diet (HFD).

Methods: Changes in lipid and glucose metabolism and androgen signaling were investigated at physiological and molecular levels in the muscle, liver, and adipose tissues of non-castrated and castrated rats under ND or HFD feeding.

Results: Castration-induced testosterone deficiency predisposed animals on ND to early development of fatty liver by activating fatty acid (FA) synthesis, whereas HFD activated hepatic FA uptake CD36 expression, leading to the development of hepatic steatosis. In rats fed ND, castration induced muscle fat accumulation by activating CD36 expression. In the subcutaneous fat of ND-fed rats, castration increased adiposity and the expression of FA synthesis-related genes, but it decreased glucose transporter gene expression. In the abdominal fat of rats fed ND, castration increased adiposity by upregulating FA synthesis-related genes, and HFD promoted adiposity by inducing FA uptake, glucose transporter, and FA synthesis-related gene expression. In rats fed ND, castration decreased body growth and muscle weight and downregulated the expression of genes androgen signaling in the longissimus dorsi muscle.

Conclusions: Testosterone deficiency increases adiposity in a tissue-specific and diet-dependent manner. Testosterone deficiency decreases body and muscle weights and downregulates androgen signaling.

Background and aim: The association with obesity of a common variant near the melanocortin-4 receptor (MC4R) gene (rs17782313) has been indicated in various studies. Adherence to dietary quality indices also have shown to have potential favorable effects on obesity-related health outcomes. However, no study has examined the interaction between rs17782313 and the Dietary Approach to Stop Hypertension (DASH) score and the Mediterranean Dietary Score (MDS) on cardio-metabolic risk factors and hypothalamic hormones. Therefore, the purpose of the current study was to examine whether adherence to these dietary quality indices modifies the association of the MC4R rs17782313 polymorphism with cardio-metabolic risk factors and hypothalamic hormones among obese adults.

Method: Two hundred eighty-eight healthy obese adults were recruited in this cross-sectional study. Diet quality indices, including DASH score and MDS, were calculated from a validated 147-item food frequency questionnaire (FFQ). MC4R s17782313 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). An ANCOVA multivariate interaction model was used to assess the gene-diet interaction.

Results: Significant interactions were detected between DASH score and MC4R rs17782313 genotypes on systolic blood pressure (SBP), atherogenic index of plasma (AIP), and serum glucose and triglyceride (TG) among the female group (p_Interaction < 0.05). In the male group, there were gene-DASH and gene-MDS interactions in relation to serum glucose concentration and plasma α-melanocyte stimulating hormone (MSH) levels, but these were found only in multi-adjusted interaction models (p_Interaction < 0.05). In addition, there was a significant interaction between MC4R rs17782313 polymorphism and DASH score on plasma agouti-related peptide (AgRP) concentrations in the female group in a multivariate interaction model (p_Interaction < 0.05). An inverse association between DASH score and chance of having the CC genotype in a multivariate-adjusted model among women was also revealed.

Conclusion: MC4R rs17782313 interacts with healthy dietary pattern (DASH score and MDS) to influence cardio-metabolic risk factors and hypothalamic hormones in obese individuals. Prospective cohort studies are needed to further assess these findings.

Background: Adiponectin and resistin are typically secreted by the adipose tissue and are abnormally expressed in obesity. However, the underlying influential factors and mechanisms are to be elucidated. It is well known that the expression of genes is regulated by epigenetics while gut microbiota participates in epigenetic processes through its metabolites such as folate, biotin, and short-chain fatty acids (SCFAs). Therefore, we supposed that alteration of gut microbiota might affect the transcriptional expression of adiponectin and resistin through epigenetic regulation in obesity.

Methods: C57BL/6J mice were fed either a high-fat diet (34.9% fat by wt., 60% kcal) or a normal-fat diet (4.3% fat by wt., 10% kcal) for 16 weeks, with ampicillin and neomycin delivered via drinking water to interfere with gut microbiota development. Fecal microbiota was analyzed by 16S rRNA high-throughput sequencing. The mRNA expression levels of genes were measured by real-time quantitative RT-PCR. SCFA contents in feces were examined using gas chromatography.

Results: Alteration of the gut microbiota induced by antibiotic use, characterized by a dramatic reduction of the phylum Firmicutes and Actinobacteria and an increase of Proteobacteria with reductions of genera including Lactobacillus, norank_f_Bacteroidales_S24-7_group, Alistipes, Desulfovibrio, Helicobacter, etc., and increases in Bacteroides, Enterobacter, Klebsiella, inhibited the body weight gain in mice fed the high-fat diet instead of the normal-fat diet. The mRNA expression of adiponectin and resistin was upregulated by antibiotic use in mice fed the high-fat diet, accompanied by increased expression of fat oxidation and thermogenesis-related genes (PPAR-α, Pgc-1α, and Atgl) in the fat and/or liver, whereas no change in the expression of adiponectin and resistin was found in mice fed the normal-fat diet. Furthermore, antibiotic use reduced DNA methylation fractions of the adiponectin and resistin promoters and downregulated the expression of DNA methyltransferase 1 and 3a (DNMT1 and DNMT3a) with the high-fat diet feeding.

Conclusion: Alteration of gut microbiota induced by antibiotic use may affect the expression of adiponectin and resistin in mice fed the high-fat diet by modifying promoter DNA methylation, thus leading to increased fatty acid oxidation and less body weight gain.