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母体肥胖通过特定脂肪组织的表观遗传修饰程序化增加雄性子代大鼠瘦素基因的表达。

Maternal obesity programs increased leptin gene expression in rat male offspring via epigenetic modifications in a depot-specific manner.

机构信息

Univ. Lille, EA4489, Équipe Malnutrition Maternelle et Programmation des Maladies Métaboliques, F-59000 Lille, France.

UMR BDR, INRA, ENVA, Université Paris Saclay, 78350, Jouy-en-Josas, France; UVSQ, Université Versailles-Saint-Quentin-en-Yvelines, France.

出版信息

Mol Metab. 2017 May 31;6(8):922-930. doi: 10.1016/j.molmet.2017.05.010. eCollection 2017 Aug.

DOI:10.1016/j.molmet.2017.05.010
PMID:28752055
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5518658/
Abstract

OBJECTIVE

According to the Developmental Origin of Health and Disease (DOHaD) concept, maternal obesity and accelerated growth in neonates predispose offspring to white adipose tissue (WAT) accumulation. In rodents, adipogenesis mainly develops during lactation. The mechanisms underlying the phenomenon known as developmental programming remain elusive. We previously reported that adult rat offspring from high-fat diet-fed dams (called HF) exhibited hypertrophic adipocyte, hyperleptinemia and increased leptin mRNA levels in a depot-specific manner. We hypothesized that leptin upregulation occurs via epigenetic malprogramming, which takes place early during development of WAT.

METHODS

As a first step, we identified two potential enhancers located upstream and downstream of the leptin transcription start site that exhibit strong dynamic epigenomic remodeling during adipocyte differentiation. We then focused on epigenetic modifications (methylation, hydroxymethylation, and histone modifications) of the promoter and the two potential enhancers regulating leptin gene expression in perirenal (pWAT) and inguinal (iWAT) fat pads of HF offspring during lactation (postnatal days 12 (PND12) and 21 (PND21)) and in adulthood.

RESULTS

PND12 is an active period for epigenomic remodeling in both deposits especially in the upstream enhancer, consistent with leptin gene induction during adipogenesis. Unlike iWAT, some of these epigenetic marks were still observable in pWAT of weaned HF offspring. Retained marks were only visible in pWAT of 9-month-old HF rats that showed a persistent "expandable" phenotype.

CONCLUSIONS

Consistent with the DOHaD hypothesis, persistent epigenetic remodeling occurs at regulatory regions especially within intergenic sequences, linked to higher leptin gene expression in adult HF offspring in a depot-specific manner.

摘要

目的

根据健康与疾病的发育起源(DOHaD)概念,母体肥胖和新生儿生长加速使后代易发生白色脂肪组织(WAT)堆积。在啮齿动物中,脂肪生成主要在哺乳期发育。发育编程现象的机制仍不清楚。我们之前报道过,高脂肪饮食喂养的母鼠的成年大鼠后代(称为 HF)表现出脂肪细胞肥大、高瘦素血症和脂肪特异性瘦素 mRNA 水平升高。我们假设瘦素的上调是通过表观遗传编程发生的,这种编程发生在 WAT 发育的早期。

方法

作为第一步,我们鉴定了位于瘦素转录起始位点上游和下游的两个潜在增强子,它们在脂肪细胞分化过程中表现出强烈的动态表观基因组重塑。然后,我们专注于哺乳期(出生后第 12 天(PND12)和 21 天(PND21))和成年期的 HF 后代肾周(pWAT)和腹股沟(iWAT)脂肪垫中调节瘦素基因表达的启动子和两个潜在增强子的表观遗传修饰(甲基化、羟甲基化和组蛋白修饰)。

结果

PND12 是两个沉积中表观基因组重塑的活跃时期,特别是在上游增强子中,与脂肪生成过程中的瘦素基因诱导一致。与 iWAT 不同,这些表观遗传标记中的一些在断奶后的 HF 后代的 pWAT 中仍然可见。在表现出持续“可扩张”表型的 9 月龄 HF 大鼠的 pWAT 中仅可见保留的标记。

结论

与 DOHaD 假说一致,持续的表观遗传重塑发生在调节区域,特别是基因间序列内,与脂肪特异性的成年 HF 后代中更高的瘦素基因表达有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e355/5518658/7bd2943e03c2/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e355/5518658/ff89c2fba2dd/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e355/5518658/d1451088b291/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e355/5518658/b9a591971f5a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e355/5518658/7bd2943e03c2/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e355/5518658/ff89c2fba2dd/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e355/5518658/d1451088b291/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e355/5518658/b9a591971f5a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e355/5518658/7bd2943e03c2/gr4.jpg

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2
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Int J Obes (Lond). 2017 Apr;41(4):652-659. doi: 10.1038/ijo.2017.8. Epub 2017 Feb 21.
3
The expanding problem of adipose depot remodeling and postnatal adipocyte progenitor recruitment.
脂肪组织中瘦素上游增强子表观遗传修饰的性别特异性作用。
Clin Epigenetics. 2025 Feb 11;17(1):21. doi: 10.1186/s13148-025-01830-2.
4
Diabetes Mellitus and Pregnancy: An Insight into the Effects on the Epigenome.糖尿病与妊娠:对表观基因组影响的洞察
Biomedicines. 2024 Feb 2;12(2):351. doi: 10.3390/biomedicines12020351.
5
The Impact of Maternal Obesity on Adipose Progenitor Cells.母体肥胖对脂肪祖细胞的影响。
Biomedicines. 2023 Dec 8;11(12):3252. doi: 10.3390/biomedicines11123252.
6
Transcriptional and epigenetic changes after dietary and surgical weight loss interventions in an animal model of obesity.肥胖动物模型中饮食和手术减肥干预后的转录和表观遗传变化。
Int J Obes (Lond). 2024 Jan;48(1):103-110. doi: 10.1038/s41366-023-01395-1. Epub 2023 Oct 13.
7
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8
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脂肪储存重塑和出生后脂肪细胞祖细胞募集这一不断扩大的问题。
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5
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PLoS One. 2016 May 12;11(5):e0154949. doi: 10.1371/journal.pone.0154949. eCollection 2016.
6
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J Endocrinol. 2016 Jul;230(1):39-53. doi: 10.1530/JOE-16-0037. Epub 2016 Apr 27.
7
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J Physiol. 2016 Aug 1;594(15):4453-66. doi: 10.1113/JP272123. Epub 2016 May 29.
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9
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