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Mediation Analysis Supports a Causal Relationship between Maternal Hyperglycemia and Placental DNA Methylation Variations at the Leptin Gene Locus and Cord Blood Leptin Levels

中介分析支持孕妇高血糖与瘦素基因位点胎盘 DNA 甲基化变异和脐血瘦素水平之间的因果关系。

  • 影响因子:4.32
  • DOI:10.3390/ijms21010329
  • 作者列表:"Valérie Gagné-Ouellet","Edith Breton","Kathrine Thibeault","Carol-Ann Fortin","Andres Cardenas","Renée Guérin","Patrice Perron","Marie-France Hivert","Luigi Bouchard
  • 发表时间:2020-01-24
Abstract

Changes in fetal DNA methylation (DNAm) of the leptin (LEP) gene have been associated with exposure to maternal hyperglycemia, but their links with childhood obesity risk are still unclear. We investigated the association between maternal hyperglycemia, placental LEP DNAm (25 5&#8242;-C-phosphate-G-3&#8242; (CpG) sites), neonatal leptinemia, and adiposity (i.e., BMI and skinfold thickness (ST) (subscapular (SS) + triceps (TR) skinfold measures, and the ratio of SS:TR) at 3-years-old, in 259 mother&#8722;child dyads, from Gen3G birth cohort. We conducted multivariate linear analyses adjusted for gestational age at birth, sex of the child, age at follow-up, and cellular heterogeneity. We assessed the causal role of DNAm in the association between maternal glycemia and childhood outcomes, using mediation analysis. We found three CpGs associated with neonatal leptinemia (p &#8804; 0.002). Of these, cg05136031 and cg15758240 were also associated with BMI (&#946; = &#8722;2.69, p = 0.05) and fat distribution (&#946; = &#8722;0.581, p = 0.05) at 3-years-old, respectively. Maternal glycemia was associated with DNAm at cg15758240 (&#946; = &#8722;0.01, p = 0.04) and neonatal leptinemia (&#946; = 0.19, p = 0.004). DNAm levels at cg15758240 mediates 0.8% of the association between maternal glycemia and neonatal leptinemia (p < 0.001). Our results support that DNAm regulation of the leptin pathway in response to maternal glycemia might be involved in programming adiposity in childhood.

摘要

瘦素 (LEP) 基因胎儿 DNA 甲基化 (DNAm) 的变化与母体高血糖暴露相关,但其与儿童肥胖风险的联系仍不清楚。我们调查了产妇高血糖、胎盘 LEP DNAm (25 5 &amp; #8242;-C-phosphate-G-3 &amp; #8242; (CpG) 位点) 、新生儿瘦素血症和肥胖 (i。 e.,3 岁时 BMI 和皮褶厚度 (ST) (肩胛下 (SS) + 三头肌 (TR) 皮褶测量,以及 SS: TR 的比值), 在 259 个母亲 &amp; #8722; 儿童二胎中,来自 Gen3G 出生队列。我们进行了多变量线性分析,校正了出生胎龄、患儿性别、随访年龄和细胞异质性。我们使用中介分析评估了 DNAm 在母体血糖和儿童期结局之间关联中的因果作用。我们发现 3 个 cpg 与新生儿瘦素血症相关 (p &amp; #8804; 0.002)。其中,cg05136031 和 cg15758240 也与 BMI (&amp; #946; = &amp; #8722; 2.69,p = 0.05) 和脂肪分布 (&amp; #946; = &amp; #8722; 0.581, p = 0.05) 分别在 3 岁。产妇血糖与 DNAm 在 cg15758240 ( 946; = &amp; #8722; 0.01,p = 0.04) 和新生儿钩端螺旋菌血症 ( 946; = 0.19,p = 0.004) 相关。Cg15758240 的 DNAm 水平介导了母亲血糖与新生儿钩端螺旋体血症之间 0.8% 的相关性 (p

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影响因子:4.51
发表时间:2020-01-24
来源期刊:Nutrients
DOI:10.3390/nu12010090
作者列表:["Stephen Morehen","Benoit Smeuninx","Molly Perkins","Paul Morgan","Leigh Breen"]

METHODS:Maintaining adequate daily protein intake is important to maintain muscle mass throughout the lifespan. In this regard, the overnight period has been identified as a window of opportunity to increase protein intake in the elderly. However, it is unknown whether pre-sleep protein intake affects next-morning appetite and, consequently, protein intake. Therefore, the purpose of the current study was to investigate the effects of a pre-sleep protein drink on next-morning appetite, energy intake and metabolism. Twelve older individuals (eight males, four females; age: 71.3 ± 4.2 years) took part in a single-blind randomised cross-over study. After a standardised dinner, participants consumed either a 40-g protein drink, isocaloric maltodextrin drink, or placebo water control before bedtime. Next-morning appetite, energy intake, resting metabolic rate (RMR), respiratory exchange rate (RER), and plasma acylated ghrelin, leptin, glucose, and insulin concentrations were assessed. No between-group differences were observed for appetite and energy intake at breakfast. Furthermore, RMR, RER, and assessed blood markers were not significantly different between any of the treatment groups. Pre-sleep protein intake does not affect next-morning appetite and energy intake and is therefore a viable strategy to increase daily protein intake in an older population.

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影响因子:4.32
发表时间:2020-01-24
DOI:10.3390/ijms21010123
作者列表:["Tzi-Peng Yang","Hsiao-Mei Chen","Chao-Chin Hu","Li-Yuan Chen","Fen-Fen Shih","Disline Manli Tantoh","Kuan-Jung Lee","Yi-Chia Liaw","Rong-Tzong Tsai","Yung-Po Liaw"]

METHODS:Leptin (LEP) regulates glucose metabolism and energy storage in the body. Osteoarthritis (OA) is associated with the upregulation of serum LEP. LEP promoter methylation is associated with obesity. So far, few studies have explored the association of BMI and OA with LEP methylation. We assessed the interaction between body mass index (BMI) and OA on LEP promoter methylation. Data of 1114 participants comprising 583 men and 558 women, aged 30&#8722;70 years were retrieved from the Taiwan Biobank Database (2008&#8722;2015). Osteoarthritis was self-reported and cases were those who reported having ever been clinically diagnosed with osteoarthritis. BMI was categorized into underweight, normal weight, overweight, and obesity. The mean LEP promoter methylation level in individuals with osteoarthritis was 0.5509 &#177; 0.00437 and 0.5375 &#177; 0.00101 in those without osteoarthritis. The interaction between osteoarthritis and BMI on LEP promoter methylation was significant (p-value = 0.0180). With normal BMI as the reference, the mean LEP promoter methylation level was significantly higher in obese osteoarthritic individuals (&#946; = 0.03696, p-value = 0.0187). However, there was no significant association between BMI and LEP promoter methylation in individuals without osteoarthritis, regardless of BMI. In conclusion, only obesity was significantly associated with LEP promoter methylation (higher levels) specifically in osteoarthritic patients.

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影响因子:4.82
发表时间:2020-01-01
DOI:10.1038/s41366-019-0368-2
作者列表:["Wulan, Siti N.","Schrauwen-Hinderling, Vera B.","Westerterp, Klaas R.","Plasqui, Guy"]

METHODS:Background For the same BMI, South Asians have a higher body fat percentage, a higher liver fat content and a more adverse metabolic profile than whites. South Asians may have a lower fat oxidation than whites, which could result in an unfavorable metabolic profile when exposed to increased high-fat foods consumption and decreased physical activity as in current modern lifestyle. Objective To determine substrate partitioning, liver fat accumulation and metabolic profile in South Asian and white men in response to overfeeding with high-fat diet under sedentary conditions in a respiration chamber. Design Ten South Asian men (BMI, 18–29 kg/m^2) and 10 white men (BMI, 22–33 kg/m^2), matched for body fat percentage, aged 20–40 year were included. A weight maintenance diet (30% fat, 55% carbohydrate, and 15% protein) was given for 3 days. Thereafter, a baseline measurement of liver fat content (1H-MRS) and blood parameters was performed. Subsequently, subjects were overfed (150% energy requirement) with a high-fat diet (60% fat, 25% carbohydrate, and 15% protein) over 3 consecutive days while staying in a respiration chamber mimicking a sedentary lifestyle. Energy expenditure and substrate use were measured for 3 × 24-h. Liver fat and blood parameters were measured again after the subjects left the chamber. Results The 24-h fat oxidation as a percentage of total energy expenditure did not differ between ethnicities ( P  = 0.30). Overfeeding increased liver fat content ( P  = 0.02), but the increase did not differ between ethnicities ( P  = 0.64). In South Asians, overfeeding tended to increase LDL-cholesterol ( P  = 0.08), tended to decrease glucose clearance ( P  = 0.06) and tended to elevate insulin response ( P  = 0.07) slightly more than whites. Conclusions Despite a similar substrate partitioning and similar accretion of liver fat, overfeeding with high-fat under sedentary conditions tended to have more adverse effects on the lipid profile and insulin sensitivity in South Asians.

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