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Effects of excess sugars and lipids on the growth and development of Caenorhabditis elegans. 过量糖和脂对秀丽隐杆线虫生长发育的影响。
Pub Date : 2020-01-29 eCollection Date: 2020-01-01 DOI: 10.1186/s12263-020-0659-1
Xiong Wang, Lin Zhang, Lei Zhang, Wenli Wang, Sihan Wei, Jie Wang, Huilian Che, Yali Zhang

Background: Excessive intake of carbohydrates and fats causes over-nutrition, leading to a variety of diseases and complications. Here, we characterized the effects of different types of sugar and lipids on the growth and development of Caenorhabditis elegans.

Methods: We measured the lifespan, reproductive capacity, and length of nematodes after sugars and lipids treatment alone and co-treatment of sugars and lipids. Furthermore, we studied the mechanisms underlying the damage caused by high-sucrose and high-stearic acid on C.elegans by using transcriptome sequencing technology.

Results: The results showed that a certain concentration of sugar and lipid promoted the growth and development of nematodes. However, excessive sugars and lipids shortened the lifespan and length of nematodes and destroyed their reproductive capacity. Based on the results of the orthogonal test, we selected 400 mmol/L sucrose and 500 μg/mL stearic acid to model a high-sugar and high-lipid diet for C. elegans.

Conclusion: High-sugar and high-lipid intake altered the expression of genes involved in biofilm synthesis, genes that catalyze the synthesis and degradation of endogenous substances, and genes involved in innate immunity, resulting in physiological damage. Furthermore, we explored the protective effect of resveratrol on high-sugar and high-lipid damage to nematodes. Resveratrol plays a role in repairing by participating in the metabolism of foreign substances and reducing cellular oxidative stress.

背景:过量摄入碳水化合物和脂肪会导致营养过剩,导致多种疾病和并发症。在这里,我们描述了不同类型的糖和脂类对秀丽隐杆线虫生长发育的影响。方法:我们测量了糖和脂质单独处理和糖和脂质共同处理后线虫的寿命、生殖能力和长度。此外,我们利用转录组测序技术研究了高蔗糖和高硬脂酸对秀丽隐杆线虫的损伤机制。结果:一定浓度的糖和脂类对线虫的生长发育有促进作用。然而,过量的糖和脂会缩短线虫的寿命和长度,并破坏它们的繁殖能力。在正交试验的基础上,选择400 mmol/L蔗糖和500 μg/mL硬脂酸,建立秀丽隐杆线虫高糖高脂日粮模型。结论:高糖高脂摄入改变了生物膜合成相关基因、内源性物质合成与降解催化基因、先天免疫相关基因的表达,导致生理损伤。此外,我们还探讨了白藜芦醇对线虫高糖、高脂损伤的保护作用。白藜芦醇通过参与外来物质的代谢和减少细胞氧化应激,起到修复作用。
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引用次数: 23
Biomarkers of meat and seafood intake: an extensive literature review. 肉类和海鲜摄入量的生物标志物:广泛的文献综述。
Pub Date : 2019-12-30 eCollection Date: 2019-01-01 DOI: 10.1186/s12263-019-0656-4
Cătălina Cuparencu, Giulia Praticó, Lieselot Y Hemeryck, Pedapati S C Sri Harsha, Stefania Noerman, Caroline Rombouts, Muyao Xi, Lynn Vanhaecke, Kati Hanhineva, Lorraine Brennan, Lars O Dragsted

Meat, including fish and shellfish, represents a valuable constituent of most balanced diets. Consumption of different types of meat and fish has been associated with both beneficial and adverse health effects. While white meats and fish are generally associated with positive health outcomes, red and especially processed meats have been associated with colorectal cancer and other diseases. The contribution of these foods to the development or prevention of chronic diseases is still not fully elucidated. One of the main problems is the difficulty in properly evaluating meat intake, as the existing self-reporting tools for dietary assessment may be imprecise and therefore affected by systematic and random errors. Dietary biomarkers measured in biological fluids have been proposed as possible objective measurements of the actual intake of specific foods and as a support for classical assessment methods. Good biomarkers for meat intake should reflect total dietary intake of meat, independent of source or processing and should be able to differentiate meat consumption from that of other protein-rich foods; alternatively, meat intake biomarkers should be specific to each of the different meat sources (e.g., red vs. white; fish, bird, or mammal) and/or cooking methods. In this paper, we present a systematic investigation of the scientific literature while providing a comprehensive overview of the possible biomarker(s) for the intake of different types of meat, including fish and shellfish, and processed and heated meats according to published guidelines for biomarker reviews (BFIrev). The most promising biomarkers are further validated for their usefulness for dietary assessment by published validation criteria.

肉类,包括鱼类和贝类,是大多数均衡膳食的重要组成部分。食用不同种类的肉类和鱼类对健康既有好处也有坏处。白肉和鱼一般与积极的健康结果有关,而红肉,特别是加工肉类则与结肠直肠癌和其他疾病有关。这些食品对慢性疾病的发生或预防所起的作用仍未完全阐明。主要问题之一是难以正确评估肉类摄入量,因为现有的自我报告膳食评估工具可能不够精确,因此会受到系统误差和随机误差的影响。有人提出可以用生物液体中测量的膳食生物标志物来客观测量特定食物的实际摄入量,并为传统的评估方法提供支持。好的肉类摄入量生物标志物应能反映膳食中肉类的总摄入量,不受来源或加工方式的影响,并能区分肉类和其他富含蛋白质食物的摄入量;或者,肉类摄入量生物标志物应针对不同的肉类来源(如红肉与白肉;鱼肉、鸟肉或哺乳动物肉)和/或烹饪方法。在本文中,我们对科学文献进行了系统的调查,同时根据已公布的生物标志物审查指南(BFIrev),全面概述了不同类型肉类(包括鱼类和贝类)以及加工和加热肉类摄入量的可能生物标志物。最有前景的生物标志物将根据已公布的验证标准进一步验证其在膳食评估中的实用性。
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引用次数: 0
Current basis and future directions of zebrafish nutrigenomics. 斑马鱼营养基因组学研究的现状、基础及未来发展方向。
Pub Date : 2019-12-27 eCollection Date: 2019-01-01 DOI: 10.1186/s12263-019-0658-2
Michael B Williams, Stephen A Watts

This review investigates the current state of nutrigenomics in the zebrafish animal models. The zebrafish animal model has been used extensively in the study of disease onset and progression and associated molecular changes. In this review, we provide a synopsis of nutrigenomics using the zebrafish animal model. Obesity and dyslipidemia studies describe the genomics of dietary-induced obesity in relation to high-fat/high-calorie diets. Inflammation and cardiovascular studies describe dietary effects on the expression of acute inflammatory markers and resulting chronic inflammatory issues including atherosclerosis. We also evaluated the genomic response to bioactive dietary compounds associated with metabolic disorders. Carbohydrate metabolism and β-cell function studies describe the impacts of high-carbohydrate dietary challenges on nutritional programming. We also report tumorigenesis in relation to dietary carcinogen exposure studies that can result in permanent genomic changes. Vitamin and mineral deficiency studies demonstrate transgenerational genomic impacts of micronutrients in the diet and temporal expression changes. Circadian rhythm studies describe the relation between metabolism and natural temporal cycles of gene expression that impacts health. Bone formation studies describe the role of dietary composition that influences bone reabsorption regulation. Finally, this review provides future directions in the use of the zebrafish model for nutrigenomic and nutrigenetic research.

本文综述了斑马鱼动物模型营养基因组学的研究现状。斑马鱼动物模型已被广泛用于研究疾病的发生和进展以及相关的分子变化。本文就利用斑马鱼动物模型进行营养基因组学研究作一综述。肥胖和血脂异常研究描述了与高脂肪/高热量饮食有关的饮食引起的肥胖的基因组学。炎症和心血管研究描述了饮食对急性炎症标志物表达的影响,并由此导致包括动脉粥样硬化在内的慢性炎症问题。我们还评估了与代谢紊乱相关的生物活性膳食化合物的基因组反应。碳水化合物代谢和β细胞功能研究描述了高碳水化合物饮食挑战对营养规划的影响。我们还报道了与饮食致癌物暴露研究相关的肿瘤发生,这可能导致永久性的基因组变化。维生素和矿物质缺乏研究表明,饮食中微量营养素的跨代基因组影响和时间表达变化。昼夜节律研究描述了代谢与影响健康的基因表达的自然时间周期之间的关系。骨形成研究描述了饮食成分对骨重吸收调节的影响。最后,对斑马鱼模型在营养基因组学和营养遗传学研究中的应用进行了展望。
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引用次数: 17
The peptide transporter 1a of the zebrafish Danio rerio, an emerging model in nutrigenomics and nutrition research: molecular characterization, functional properties, and expression analysis. 斑马鱼Danio rerio肽转运体1a,营养基因组学和营养研究中的新兴模型:分子表征,功能特性和表达分析。
Pub Date : 2019-12-19 eCollection Date: 2019-01-01 DOI: 10.1186/s12263-019-0657-3
Francesca Vacca, Amilcare Barca, Ana S Gomes, Aurora Mazzei, Barbara Piccinni, Raffaella Cinquetti, Gianmarco Del Vecchio, Alessandro Romano, Ivar Rønnestad, Elena Bossi, Tiziano Verri

Background: Peptide transporter 1 (PepT1, alias Slc15a1) mediates the uptake of dietary di/tripeptides in all vertebrates. However, in teleost fish, more than one PepT1-type transporter might function, due to specific whole genome duplication event(s) that occurred during their evolution leading to a more complex paralogue gene repertoire than in higher vertebrates (tetrapods).

Results: Here, we describe a novel di/tripeptide transporter in the zebrafish (Danio rerio), i.e., the zebrafish peptide transporter 1a (PepT1a; also known as Solute carrier family 15 member a1, Slc15a1a), which is a paralogue (78% similarity, 62% identity at the amino acid level) of the previously described zebrafish peptide transporter 1b (PepT1b, alias PepT1; also known as Solute carrier family 15 member 1b, Slc15a1b). Also, we report a basic analysis of the pept1a (slc15a1a) mRNA expression levels in zebrafish adult tissues/organs and embryonic/early larval developmental stages. As assessed by expression in Xenopus laevis oocytes and two-electrode voltage clamp measurements, zebrafish PepT1a, as PepT1b, is electrogenic, Na+-independent, and pH-dependent and functions as a low-affinity system, with K 0.5 values for Gly-Gln at - 60 mV of 6.92 mmol/L at pH 7.6 and 0.24 mmol/L at pH 6.5 and at - 120 mV of 3.61 mmol/L at pH 7.6 and 0.45 mmol/L at pH 6.5. Zebrafish pept1a mRNA is highly expressed in the intestine and ovary of the adult fish, while its expression in early development undergoes a complex trend over time, with pept1a mRNA being detected 1 and 2 days post-fertilization (dpf), possibly due to its occurrence in the RNA maternal pool, decreasing at 3 dpf (~ 0.5-fold) and increasing above the 1-2 dpf levels at 4 to 7 dpf, with a peak (~ 7-fold) at 6 dpf.

Conclusions: We show that the zebrafish PepT1a-type transporter is functional and co-expressed with pept1b (slc15a1b) in the adult fish intestine. Its expression is also confirmed during the early phases of development when the yolk syncytial layer is present and yolk protein resorption processes are active. While completing the missing information on PepT1-type transporters function in the zebrafish, these results open to future investigations on the similar/differential role(s) of PepT1a/PepT1b in zebrafish and teleost fish physiology.

背景:肽转运蛋白1 (PepT1,别名Slc15a1)介导所有脊椎动物对膳食二肽/三肽的摄取。然而,在硬骨鱼中,由于在进化过程中发生的特定全基因组复制事件导致比高等脊椎动物(四足动物)更复杂的旁系基因库,因此可能有不止一种pept1型转运蛋白起作用。结果:在这里,我们描述了斑马鱼(Danio rerio)中一种新的二/三肽转运蛋白,即斑马鱼肽转运蛋白1a (PepT1a;也被称为溶质载体家族15成员a1, Slc15a1a),它是前面描述的斑马鱼肽转运体1b (PepT1b,别名PepT1;也称为溶质载体家族15成员1b, Slc15a1b)。此外,我们报告了斑马鱼成年组织/器官和胚胎/早期幼虫发育阶段pept1a (slc15a1a) mRNA表达水平的基本分析。通过在非洲爪鱼卵母细胞中的表达和双电极电压钳测量来评估,斑马鱼PepT1a,即PepT1b,具有电致性、Na+无关性和pH依赖性,是一个低亲和系统,gy - gln在- 60 mV时的K值为6.92 mmol/L, pH值为7.6和0.24 mmol/L,在- 120 mV时的K值为3.61 mmol/L, pH值为7.6和0.45 mmol/L。斑马鱼pept1a mRNA在成年鱼的肠道和卵巢中高度表达,但其在发育早期的表达经历了一个复杂的趋势,在受精后1和2天(dpf)检测到pept1a mRNA,可能是由于它出现在RNA母池中,在3 dpf时下降(约0.5倍),在4至7 dpf时增加1-2 dpf,在6 dpf时达到峰值(约7倍)。结论:我们发现斑马鱼pept1a型转运体在成年鱼肠中与pept1b (slc15a1b)共表达。在卵黄合胞层存在和卵黄蛋白吸收过程活跃的发育早期,也证实了它的表达。这些结果填补了斑马鱼中pept1型转运蛋白功能的缺失信息,为进一步研究PepT1a/PepT1b在斑马鱼和硬骨鱼生理中的相似/差异作用开辟了道路。
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引用次数: 11
Endorsing the STrengthening the Reporting of Observational Studies in Epidemiology-nutritional epidemiology (STROBE-nut) statement at Genes & Nutrition. 赞同《基因与营养》杂志关于加强流行病学-营养流行病学观察性研究报告(STROBE-nut)的声明。
Pub Date : 2019-11-18 eCollection Date: 2019-01-01 DOI: 10.1186/s12263-019-0655-5
Dana Hawwash, Carl Lachat
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引用次数: 6
Effect of gestational oily fish intake on the risk of allergy in children may be influenced by FADS1/2, ELOVL5 expression and DNA methylation. 妊娠期摄入油性鱼对儿童过敏风险的影响可能受FADS1/2、ELOVL5表达和DNA甲基化的影响。
Pub Date : 2019-06-18 eCollection Date: 2019-01-01 DOI: 10.1186/s12263-019-0644-8
Purevsuren Losol, Faisal I Rezwan, Veeresh K Patil, Carina Venter, Susan Ewart, Hongmei Zhang, S Hasan Arshad, Wilfried Karmaus, John W Holloway

Background: Evidence suggests that prenatal exposure to n-3 long-chain polyunsaturated fatty acids (LCPUFA) reduces the incidence of allergic disease in children. LCPUFAs are produced from dietary precursors catalyzed by desaturases and elongases encoded by the FADS1/2 and ELOVL5 genes. DNA methylation regulates gene activity and fatty acid supplementation could alter DNA methylation (DNA-M) at these genes. We investigated whether DNA-M and expression of the FADS1/2 and ELOVL5 genes were associated with allergy in children and gestational fish intake. We studied 170 participants from the Isle of Wight 3rd Generation Cohort, UK. Phenotype data and exposure was assessed by questionnaires. Genome-wide DNA-M in cord blood samples was quantified using the Illumina Infinium HumanMethylation450 and EPIC Beadchips. Five SNPs (single-nucleotide polymorphisms) in the FADS gene cluster and one SNP in ELOVL5 were genotyped in offspring. FADS gene expression in offspring cord blood was determined.

Results: Gestational fish intake was significantly associated with increased methylation of cg12517394 (P = 0.049), which positively correlated with FADS1 mRNA levels (P = 0.021). ELOVL5 rs2397142 was significantly associated with eczema (P = 0.011) and methylation at cg11748354 and cg24524396 (P < 0.001 and P = 0.036, respectively). Gestational fish intake was strongly associated with elevated DNA-M at cg11748354 and cg24524396 (P = 0.029 and P = 0.002, respectively) and reduced ELOVL5 mRNA expression (P = 0.028).

Conclusion: The association between induced FADS1/2 and ELOVL5 DNA-M and reduced gene expression due to gestational fish intake provide a mechanistic explanation of the previously observed association between maternal LCPUFA intake and allergy development in early childhood.

背景:有证据表明,产前暴露于n-3长链多不饱和脂肪酸(LCPUFA)可降低儿童过敏性疾病的发生率。LCPUFAs是由FADS1/2和ELOVL5基因编码的去饱和酶和延长酶催化的饮食前体产生的。DNA甲基化调节基因活性,脂肪酸补充可以改变这些基因的DNA甲基化(DNA- m)。我们研究了DNA-M和FADS1/2和ELOVL5基因的表达是否与儿童过敏和妊娠期鱼类摄入有关。我们研究了来自英国怀特岛第三代队列的170名参与者。表型数据和暴露通过问卷进行评估。使用Illumina Infinium HumanMethylation450和EPIC Beadchips对脐带血样本的全基因组DNA-M进行定量。FADS基因簇中的5个SNP(单核苷酸多态性)和ELOVL5基因簇中的1个SNP在后代中进行了基因分型。测定FADS基因在子代脐带血中的表达。结果:妊娠鱼采食量与cg12517394甲基化升高显著相关(P = 0.049),与FADS1 mRNA水平呈正相关(P = 0.021)。ELOVL5 rs2397142与湿疹(P = 0.011)和cg11748354和cg24524396位点的甲基化显著相关(P = 0.036)。妊娠期采食鱼与cg11748354和cg24524396的DNA-M升高(P = 0.029和P = 0.002)和ELOVL5 mRNA表达降低(P = 0.028)密切相关。结论:妊娠期摄入鱼类诱导的FADS1/2和ELOVL5 DNA-M与基因表达降低之间的关联,为先前观察到的母体LCPUFA摄入与儿童早期过敏发展之间的关联提供了机制解释。
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引用次数: 0
Interaction between the amount of dietary protein and the environmental temperature on the expression of browning markers in adipose tissue of rats. 饲粮蛋白质量与环境温度对大鼠脂肪组织褐变标志物表达的相互作用。
Pub Date : 2019-06-04 eCollection Date: 2019-01-01 DOI: 10.1186/s12263-019-0642-x
Gabriela Alemán, Ana Laura Castro, Ana Vigil-Martínez, Ivan Torre-Villalvazo, Andrea Díaz-Villaseñor, Lilia G Noriega, Isabel Medina-Vera, Guillermo Ordáz, Nimbe Torres, Armando R Tovar

Background: A low-protein diet increases the expression and circulating concentration of FGF21. FGF21 stimulates the browning process of WAT by enhancing the expression of UCP1 coupled with an increase in PGC1α. Interestingly, the consumption of a low-protein diet could stimulate WAT differentiation into beige/brite cells by increasing FGF21 expression and Ucp1 mRNA abundance. However, whether the stimulus of a low-protein diet on WAT browning can synergistically interact with another browning stimulus, such as cold exposure, remains elusive.

Results: In the present study, rats were fed 6% (low), 20% (adequate), or 50% (high) dietary protein for 10 days and subsequently exposed to 4 °C for 72 h. Body weight, food intake, and energy expenditure were measured, as well as WAT browning and BAT thermogenesis markers and FGF21 circulating levels. The results showed that during cold exposure, the consumption of a high-protein diet reduced UCP1, TBX1, Cidea, Cd137, and Prdm16 in WAT when compared with the consumption of a low-protein diet. In contrast, at room temperature, a low-protein diet increased the expression of UCP1, Cidea, and Prdm16 associated with an increase in FGF21 expression and circulating levels when compared with a consumption of a high-protein diet. Consequently, the consumption of a low-protein diet increased energy expenditure.

Conclusions: These results indicate that in addition to the environmental temperature, WAT browning is nutritionally modulated by dietary protein, affecting whole-body energy expenditure.

Graphical abstract:

背景:低蛋白饮食增加FGF21的表达和循环浓度。FGF21通过增强UCP1的表达和PGC1α的增加来刺激WAT的褐变过程。有趣的是,低蛋白饮食可以通过增加FGF21表达和Ucp1 mRNA丰度来刺激WAT分化为米色/白色细胞。然而,低蛋白饮食对WAT褐变的刺激是否能与另一种褐变刺激(如冷暴露)协同作用,尚不清楚。结果:在本研究中,大鼠分别饲喂6%(低)、20%(足)或50%(高)膳食蛋白10天,随后在4°C下暴露72小时。测量体重、食物摄入量和能量消耗,以及WAT褐变和BAT产热标志物和FGF21循环水平。结果表明,在冷暴露期间,与低蛋白饮食相比,高蛋白饮食减少了WAT中的UCP1、TBX1、Cidea、Cd137和Prdm16。相比之下,在室温下,与高蛋白饮食相比,低蛋白饮食增加了UCP1、Cidea和Prdm16的表达,并增加了FGF21的表达和循环水平。因此,低蛋白饮食增加了能量消耗。结论:上述结果表明,除环境温度外,WAT褐变还受膳食蛋白质的营养调节,影响全身能量消耗。图形化的简介:
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引用次数: 11
Herbs and Spices- Biomarkers of Intake Based on Human Intervention Studies - A Systematic Review. 草药和香料-基于人为干预研究的摄入生物标志物-系统综述。
Pub Date : 2019-05-22 eCollection Date: 2019-01-01 DOI: 10.1186/s12263-019-0636-8
Rosa Vázquez-Fresno, Albert Remus R Rosana, Tanvir Sajed, Tuviere Onookome-Okome, Noah A Wishart, David S Wishart

Culinary herbs and spices have been used as both food flavoring and food preservative agents for centuries. Moreover, due to their known and presumptive health benefits, herbs and spices have also been used in medical practices since ancient times. Some of the health effects attributed to herbs and spices include antioxidant, anti-microbial, and anti-inflammatory effects as well as potential protection against cardiovascular disease, neurodegeneration, type 2 diabetes, and cancer. While interest in herbs and spices as medicinal agents remains high and their use in foods continues to grow, there have been remarkably few studies that have attempted to track the dietary intake of herbs and spices and even fewer that have tried to find potential biomarkers of food intake (BFIs). The aim of the present review is to systematically survey the global literature on herbs and spices in an effort to identify and evaluate specific intake biomarkers for a representative set of common herbs and spices in humans. A total of 25 herbs and spices were initially chosen, including anise, basil, black pepper, caraway, chili pepper, cinnamon, clove, cumin, curcumin, dill, fennel, fenugreek, ginger, lemongrass, marjoram, nutmeg, oregano, parsley, peppermint and spearmint, rosemary, saffron, sage, tarragon, and thyme. However, only 17 of these herbs and spices had published, peer-reviewed studies describing potential biomarkers of intake. In many studies, the herb or spice of interest was administrated in the form of a capsule or extract and very few studies were performed with actual foods. A systematic assessment of the candidate biomarkers was also performed. Given the limitations in the experimental designs for many of the published studies, further work is needed to better evaluate the identified set of BFIs. Although the daily intake of herbs and spices is very low compared to most other foods, this important set of food seasoning agents should not be underestimated, especially given their potential benefits to human health.

几个世纪以来,烹饪用草药和香料一直被用作食品调味剂和食品防腐剂。此外,由于它们已知的和假定的健康益处,草药和香料自古以来也被用于医疗实践。草药和香料对健康的影响包括抗氧化、抗微生物和抗炎作用,以及对心血管疾病、神经变性、2型糖尿病和癌症的潜在保护。尽管人们对草药和香料作为药物的兴趣仍然很高,而且它们在食品中的应用也在不断增长,但很少有研究试图追踪草药和香料的饮食摄入量,而试图找到潜在的食物摄入生物标志物(bfi)的研究就更少了。本综述的目的是系统地调查全球有关草药和香料的文献,以确定和评估人类常用草药和香料的一组代表性的特定摄入生物标志物。最初总共选择了25种草药和香料,包括八角、罗勒、黑胡椒、香菜、辣椒、肉桂、丁香、孜然、姜黄素、莳萝、茴香、葫芦巴、生姜、柠檬草、马郁兰、肉豆蔻、牛至、欧芹、薄荷和绿薄荷、迷迭香、藏红花、鼠尾草、龙蒿和百里香。然而,这些草药和香料中只有17种发表过同行评议的研究,描述了摄入的潜在生物标志物。在许多研究中,感兴趣的草药或香料以胶囊或提取物的形式给药,很少有研究是用实际的食物进行的。还对候选生物标志物进行了系统评估。考虑到许多已发表研究的实验设计的局限性,需要进一步的工作来更好地评估已确定的一组bfi。虽然与大多数其他食物相比,草药和香料的每日摄入量非常低,但这组重要的食品调味剂不应被低估,特别是考虑到它们对人体健康的潜在益处。
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引用次数: 72
Maternal dietary glycaemic change during gestation influences insulin-related gene methylation in the placental tissue: a genome-wide methylation analysis. 妊娠期母体饮食血糖变化影响胎盘组织中胰岛素相关基因甲基化:全基因组甲基化分析
Pub Date : 2019-05-09 eCollection Date: 2019-01-01 DOI: 10.1186/s12263-019-0634-x
Weili Yan, Yi Zhang, Liping Wang, Wenhong Yang, Chunying Li, Liling Wang, Ping Gu, Yingqian Xia, Juhua Yan, Ying Shen, Qian Zhao, Dayan Niu, Kai Mu, Yuan Jiang

Background: Studies have shown that the effects of maternal nutrition exposure during gestation influence metabolic risk in early life through an epigenetic mechanism. Low glycaemic index (GI) diets benefit both maternal and neonatal gestational outcomes. We hypothesize that maternal dietary GI or glycaemic load (GL) changes during pregnancy impact placental DNA methylation, especially in insulin resistance-related genes.

Methods: From a clinical trial of overweight pregnant women, 12 subjects who successfully reduced their GI and another 12 whose GI increased despite the intervention were selected. A genome-wide differential methylation analysis of placental tissue DNA was conducted, followed by bioinformatic annotation and validation analysis. The distribution of genome-wide differentially methylated regions (DMRs) and CpG sites was described. Six CpG sites in regulatory regions of four insulin-related genes (PLIN1, CPT1B, SSTR4, and CIDEA) were selectively validated by pyrosequencing. Pairwise Spearman correlation analysis was performed to test methylation-phenotype association in an additional 153 subjects from the same trial. Correlation between methylation of significant sites and placental mRNA expression of SSTR4 was also analysed.

Results: Dietary GI decreased by 24.3 (26.2-20.1) in the group who responded appropriately to the intervention and increased by 19.6 (15.2-29.1) in the comparison group. Epigenome-wide analysis identified 108 DMRs and 365 CpG sites with P < 0.05 adjusted by false discovery rate, distributed over all chromosomes. The methylation level of cg05009389 in the 3' UTR of PLIN1 was negatively correlated with maternal weight gain (ρ = - 0.21, P = 0.027) and increase in insulin levels (ρ = - 0.24, P = 0.015) during gestation. Methylation levels of cg17586860 and cg18197392 in the 5' UTR region of SSTR4 were negatively correlated with changes in dietary carbohydrate intake (ρ = - 0.24, Ps ≤ 0.006) and GL across gestation (ρ = - 0.23, Ps ≤ .008). This correlation survived the adjustment for maternal factors such as dietary GI, body mass index, and gestational diabetes. Up to 89% of cg18197392 methylation was explained by GL change. Cg14631053 methylation correlated positively with mRNA expression of SSTR4 in the placenta (ρ = 0.20, P = 0.037).

Conclusions: We provide the first evidence that maternal dietary GI changes during gestation may impact placental DNA methylation of insulin regulation genes. This supports the hypothesis that placental methylation may be the epigenetic mechanism through which maternal diet influences the metabolic health of offspring.

背景:研究表明,妊娠期母体营养暴露的影响通过表观遗传机制影响生命早期代谢风险。低血糖指数(GI)饮食有利于产妇和新生儿的妊娠结局。我们假设孕妇在怀孕期间饮食GI或血糖负荷(GL)的变化会影响胎盘DNA甲基化,尤其是胰岛素抵抗相关基因。方法:从一项超重孕妇临床试验中,选择12例GI降低成功的孕妇和12例干预后GI升高的孕妇。对胎盘组织DNA进行全基因组差异甲基化分析,然后进行生物信息学注释和验证分析。描述了全基因组差异甲基化区(DMRs)和CpG位点的分布。4个胰岛素相关基因(PLIN1、CPT1B、SSTR4和CIDEA)调控区域的6个CpG位点通过焦磷酸测序选择性验证。对来自同一试验的另外153名受试者进行了配对Spearman相关分析,以测试甲基化-表型关联。我们还分析了显著位点甲基化与胎盘SSTR4 mRNA表达的相关性。结果:适当干预组饮食GI下降24.3(26.2-20.1),对照组饮食GI上升19.6(15.2-29.1)。全表观基因组分析发现,pplin1与妊娠期母亲体重增加(ρ = - 0.21, P = 0.027)和胰岛素水平升高(ρ = - 0.24, P = 0.015)呈负相关,DMRs位点108个,CpG位点365个。SSTR4 5′UTR区cg17586860和cg18197392甲基化水平与妊娠期饮食碳水化合物摄入量(ρ = - 0.24, Ps≤0.006)和GL变化呈负相关(ρ = - 0.23, Ps≤0.008)。这种相关性在调整饮食GI、体重指数和妊娠糖尿病等母体因素后仍然存在。高达89%的cg18197392甲基化是由GL变化解释的。Cg14631053甲基化与胎盘中SSTR4 mRNA表达呈正相关(ρ = 0.20, P = 0.037)。结论:我们提供了妊娠期母体饮食GI变化可能影响胎盘胰岛素调节基因DNA甲基化的第一个证据。这支持了胎盘甲基化可能是母体饮食影响后代代谢健康的表观遗传机制的假设。
{"title":"Maternal dietary glycaemic change during gestation influences insulin-related gene methylation in the placental tissue: a genome-wide methylation analysis.","authors":"Weili Yan,&nbsp;Yi Zhang,&nbsp;Liping Wang,&nbsp;Wenhong Yang,&nbsp;Chunying Li,&nbsp;Liling Wang,&nbsp;Ping Gu,&nbsp;Yingqian Xia,&nbsp;Juhua Yan,&nbsp;Ying Shen,&nbsp;Qian Zhao,&nbsp;Dayan Niu,&nbsp;Kai Mu,&nbsp;Yuan Jiang","doi":"10.1186/s12263-019-0634-x","DOIUrl":"https://doi.org/10.1186/s12263-019-0634-x","url":null,"abstract":"<p><strong>Background: </strong>Studies have shown that the effects of maternal nutrition exposure during gestation influence metabolic risk in early life through an epigenetic mechanism. Low glycaemic index (GI) diets benefit both maternal and neonatal gestational outcomes. We hypothesize that maternal dietary GI or glycaemic load (GL) changes during pregnancy impact placental DNA methylation, especially in insulin resistance-related genes.</p><p><strong>Methods: </strong>From a clinical trial of overweight pregnant women, 12 subjects who successfully reduced their GI and another 12 whose GI increased despite the intervention were selected. A genome-wide differential methylation analysis of placental tissue DNA was conducted, followed by bioinformatic annotation and validation analysis. The distribution of genome-wide differentially methylated regions (DMRs) and CpG sites was described. Six CpG sites in regulatory regions of four insulin-related genes (<i>PLIN1</i>, <i>CPT1B</i>, <i>SSTR4</i>, and <i>CIDEA</i>) were selectively validated by pyrosequencing. Pairwise Spearman correlation analysis was performed to test methylation-phenotype association in an additional 153 subjects from the same trial. Correlation between methylation of significant sites and placental mRNA expression of <i>SSTR4</i> was also analysed.</p><p><strong>Results: </strong>Dietary GI decreased by 24.3 (26.2-20.1) in the group who responded appropriately to the intervention and increased by 19.6 (15.2-29.1) in the comparison group. Epigenome-wide analysis identified 108 DMRs and 365 CpG sites with <i>P</i> < 0.05 adjusted by false discovery rate, distributed over all chromosomes. The methylation level of cg05009389 in the 3' UTR of <i>PLIN1</i> was negatively correlated with maternal weight gain (<i>ρ</i> = - 0.21, <i>P</i> = 0.027) and increase in insulin levels (<i>ρ</i> = - 0.24, <i>P</i> = 0.015) during gestation. Methylation levels of cg17586860 and cg18197392 in the 5' UTR region of <i>SSTR4</i> were negatively correlated with changes in dietary carbohydrate intake (<i>ρ</i> = - 0.24, <i>P</i>s ≤ 0.006) and GL across gestation (<i>ρ</i> = - 0.23, <i>P</i>s ≤ .008). This correlation survived the adjustment for maternal factors such as dietary GI, body mass index, and gestational diabetes. Up to 89% of cg18197392 methylation was explained by GL change. Cg14631053 methylation correlated positively with mRNA expression of <i>SSTR4</i> in the placenta (<i>ρ</i> = 0.20, <i>P</i> = 0.037)<i>.</i></p><p><strong>Conclusions: </strong>We provide the first evidence that maternal dietary GI changes during gestation may impact placental DNA methylation of insulin regulation genes. This supports the hypothesis that placental methylation may be the epigenetic mechanism through which maternal diet influences the metabolic health of offspring.</p>","PeriodicalId":12554,"journal":{"name":"Genes & Nutrition","volume":"14 ","pages":"17"},"PeriodicalIF":0.0,"publicationDate":"2019-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12263-019-0634-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37240446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 12
Weighted gene co-expression network analysis to explain the relationship between plasma total carotenoids and lipid profile. 加权基因共表达网络分析解释血浆总类胡萝卜素与血脂之间的关系。
Pub Date : 2019-05-08 eCollection Date: 2019-01-01 DOI: 10.1186/s12263-019-0639-5
Bénédicte L Tremblay, Frédéric Guénard, Benoît Lamarche, Louis Pérusse, Marie-Claude Vohl

Background: Variability in circulating carotenoids may be attributable to several factors including, among others, genetic variants and lipid profile. However, relatively few studies have considered the impact of gene expression in the inter-individual variability in circulating carotenoids. Most studies considered expression of genes individually and ignored their high degree of interconnection. Weighted gene co-expression network analysis (WGCNA) is a systems biology method used for finding gene clusters with highly correlated expression levels and for relating them to phenotypic traits. The objective of the present observational study is to examine the relationship between plasma total carotenoid concentrations and lipid profile using WGCNA.

Results: Whole blood expression levels of 533 probes were associated with plasma total carotenoids. Among the four WGCNA distinct modules identified, turquoise, blue, and brown modules correlated with plasma high-density lipoprotein cholesterol (HDL-C) and total cholesterol. Probes showing a strong association with HDL-C and total cholesterol were also the most important elements of the brown and blue modules. A total of four and 29 hub genes associated with total carotenoids were potentially related to HDL-C and total cholesterol, respectively.

Conclusions: Expression levels of 533 probes were associated with plasma total carotenoid concentrations. Using WGCNA, four modules and several hub genes related to lipid and carotenoid metabolism were identified. This integrative analysis provides evidence for the potential role of gene co-expression in the relationship between carotenoids and lipid concentrations. Further studies and validation of the hub genes are needed.

背景:循环类胡萝卜素的变异性可能归因于几个因素,其中包括遗传变异和脂质谱。然而,相对较少的研究考虑了基因表达在循环类胡萝卜素的个体间变异性中的影响。大多数研究只考虑单个基因的表达,而忽略了它们之间的高度互联。加权基因共表达网络分析(WGCNA)是一种系统生物学方法,用于发现表达水平高度相关的基因簇,并将其与表型性状联系起来。本观察性研究的目的是利用WGCNA检测血浆总类胡萝卜素浓度与血脂之间的关系。结果:533探针全血表达水平与血浆总类胡萝卜素相关。在四种不同的WGCNA模块中,绿松石色、蓝色和棕色模块与血浆高密度脂蛋白胆固醇(HDL-C)和总胆固醇相关。显示与HDL-C和总胆固醇密切相关的探针也是棕色和蓝色模块中最重要的元素。总共有4个和29个与总类胡萝卜素相关的枢纽基因分别可能与HDL-C和总胆固醇相关。结论:533探针的表达水平与血浆总类胡萝卜素浓度相关。利用WGCNA,鉴定了脂质和类胡萝卜素代谢相关的4个模块和几个枢纽基因。这一综合分析为基因共表达在类胡萝卜素和脂质浓度之间的关系中的潜在作用提供了证据。中心基因需要进一步的研究和验证。
{"title":"Weighted gene co-expression network analysis to explain the relationship between plasma total carotenoids and lipid profile.","authors":"Bénédicte L Tremblay,&nbsp;Frédéric Guénard,&nbsp;Benoît Lamarche,&nbsp;Louis Pérusse,&nbsp;Marie-Claude Vohl","doi":"10.1186/s12263-019-0639-5","DOIUrl":"https://doi.org/10.1186/s12263-019-0639-5","url":null,"abstract":"<p><strong>Background: </strong>Variability in circulating carotenoids may be attributable to several factors including, among others, genetic variants and lipid profile. However, relatively few studies have considered the impact of gene expression in the inter-individual variability in circulating carotenoids. Most studies considered expression of genes individually and ignored their high degree of interconnection. Weighted gene co-expression network analysis (WGCNA) is a systems biology method used for finding gene clusters with highly correlated expression levels and for relating them to phenotypic traits. The objective of the present observational study is to examine the relationship between plasma total carotenoid concentrations and lipid profile using WGCNA.</p><p><strong>Results: </strong>Whole blood expression levels of 533 probes were associated with plasma total carotenoids. Among the four WGCNA distinct modules identified, turquoise, blue, and brown modules correlated with plasma high-density lipoprotein cholesterol (HDL-C) and total cholesterol. Probes showing a strong association with HDL-C and total cholesterol were also the most important elements of the brown and blue modules. A total of four and 29 hub genes associated with total carotenoids were potentially related to HDL-C and total cholesterol, respectively.</p><p><strong>Conclusions: </strong>Expression levels of 533 probes were associated with plasma total carotenoid concentrations. Using WGCNA, four modules and several hub genes related to lipid and carotenoid metabolism were identified. This integrative analysis provides evidence for the potential role of gene co-expression in the relationship between carotenoids and lipid concentrations. Further studies and validation of the hub genes are needed.</p>","PeriodicalId":12554,"journal":{"name":"Genes & Nutrition","volume":"14 ","pages":"16"},"PeriodicalIF":0.0,"publicationDate":"2019-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12263-019-0639-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37240445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 9
期刊
Genes & Nutrition
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