生活方式干预前后非糖尿病性高血糖(NDH)患者脑源性神经营养因子(BDNF)编码基因外显子IV甲基化状态

IF 2.5 Q3 GENETICS & HEREDITY
H. Fachim, N. Malipatil, K. Siddals, R. Donn, Gabriela Y. Cortés, C. Dalton, J. Gibson, A. Heald
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引用次数: 0

摘要

下丘脑神经元回路中的BDNF信号被认为调节哺乳动物的食物摄入。鉴于此,我们研究了生活方式干预如何影响NDH个体的血清水平和脂肪组织和褐色皮毛中BDNF基因的DNA甲基化。总共有20名参与者在生活方式干预前/后(6个月)进行了人体测量/空腹血液测试和脂肪组织活检。从脂肪组织和灰褐色皮毛中提取DNA,亚硫酸盐转化,并使用焦磷酸测序测定BDNF基因外显子IV的甲基化水平。采用酶联免疫吸附法(ELISA)检测血清BDNF水平,提取褐皮被RNA进行基因表达分析。BDNF血清水平没有差异,但黄皮毛意味着干预后BDNF基因甲基化降低。BDNF血清水平和/或甲基化与心脏代谢标志物之间存在相关性。(i)干预前:对于BDNF甲基化,我们发现脂肪组织的平均甲基化与腰臀比呈正相关,而褐色皮毛的平均甲基化与体重呈负相关。(ii)干预后:我们发现了褐皮大衣BDNF平均甲基化与HbA1c、褐皮大衣BDNF甲基化与循环IGFBP-2、BDNF血清与胰岛素之间的相关性。已知较高的BDNF %甲基化水平可降低BNDF表达。淡黄色被毛数的下降意味着BDNF甲基化以及BDNF甲基化程度较低(因此可能较高的BDNF)与较高的HbA1c和血清IGFBP-2(作为胰岛素敏感性的标志)之间的关联,以及血清BDNF水平较低与较高的循环胰岛素之间的关联,证明了BDNF基因甲基化程度与胰岛素化和葡萄糖稳态有关,特别是在NDH个体生活方式改变后。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Methylation Status of Exon IV of the Brain-Derived Neurotrophic Factor (BDNF)-Encoding Gene in Patients with Non-Diabetic Hyperglycaemia (NDH) before and after a Lifestyle Intervention
BDNF signalling in hypothalamic neuronal circuits is thought to regulate mammalian food intake. In light of this, we investigated how a lifestyle intervention influenced serum levels and DNA methylation of BDNF gene in fat tissue and buffy coat of NDH individuals. In total, 20 participants underwent anthropometric measurements/fasting blood tests and adipose tissue biopsy pre-/post-lifestyle (6 months) intervention. DNA was extracted from adipose tissue and buffy coat, bisulphite converted, and pyrosequencing was used to determine methylation levels in exon IV of the BDNF gene. RNA was extracted from buffy coat for gene expression analysis and serum BDNF levels were measured by ELISA. No differences were found in BDNF serum levels, but buffy coat mean BDNF gene methylation decreased post-intervention. There were correlations between BDNF serum levels and/or methylation and cardiometabolic markers. (i) Pre-intervention: for BDNF methylation, we found positive correlations between mean methylation in fat tissue and waist-hip ratio, and negative correlations between mean methylation in buffy coat and weight. (ii) Post-intervention: we found correlations between BDNF mean methylation in buffy coat and HbA1c, BDNF methylation in buffy coat and circulating IGFBP-2, and BDNF serum and insulin. Higher BDNF % methylation levels are known to reduce BNDF expression. The fall in buffy coat mean BDNF methylation plus the association between lower BDNF methylation (so potentially higher BDNF) and higher HbA1c and serum IGFBP-2 (as a marker of insulin sensitivity) and between lower serum BDNF and higher circulating insulin are evidence for the degree of BDNF gene methylation being implicated in insulinisation and glucose homeostasis, particularly after lifestyle change in NDH individuals.
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来源期刊
Epigenomes
Epigenomes GENETICS & HEREDITY-
CiteScore
3.80
自引率
0.00%
发文量
38
审稿时长
11 weeks
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