肥満の解読:極度の肥満の人々で変化している800以上のDNAスイッチを特定。(decoding obesity:Researchers have identified over 800 DNA switches that are changed in people with extreme obesity. )

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2023-07-07 インペリアル・カレッジ・ロンドン(ICL)

◆研究者たちは、極端な肥満の人々の細胞と通常体重の人々の細胞を比較し、800以上のDNAスイッチが変化することを特定しました。これらのスイッチは可逆的であり、肥満やその健康上の影響に対するより効果的な治療法の鍵となる可能性があります。さらに、これらのスイッチが肥満や糖尿病に関連する500以上の遺伝子の活動を変化させることがわかりました。
◆この研究結果は、肥満を遺伝子レベルで理解し、個別化された治療法の開発につながる重要な進展です。

<関連情報>

脂肪細胞における統合的ゲノム解析により、ヒトの肥満と糖尿病におけるDNAメチル化が示唆される Integrative genomic analyses in adipocytes implicate DNA methylation in human obesity and diabetes

Liam McAllan,Damir Baranasic,Sergio Villicaña,Scarlett Brown,Weihua Zhang,Benjamin Lehne,Marco Adamo,Andrew Jenkinson,Mohamed Elkalaawy,Borzoueh Mohammadi,Majid Hashemi,Nadia Fernandes,Nathalie Lambie,Richard Williams,Colette Christiansen,Youwen Yang,Liudmila Zudina,Vasiliki Lagou,Sili Tan,Juan Castillo-Fernandez,James W. D. King,Richie Soong,Paul Elliott,James Scott,Inga Prokopenko,Inês Cebola,Marie Loh,Boris Lenhard,Rachel L. Batterham,Jordana T. Bell,John C. Chambers,Jaspal S. Kooner & William R. Scott
Nature Communications  Published:15 May 2023
DOI:https://doi.org/10.1038/s41467-023-38439-z

肥満の解読:極度の肥満の人々で変化している800以上のDNAスイッチを特定。(decoding obesity:Researchers have identified over 800 DNA switches that are changed in people with extreme obesity. )

Abstract

DNA methylation variations are prevalent in human obesity but evidence of a causative role in disease pathogenesis is limited. Here, we combine epigenome-wide association and integrative genomics to investigate the impact of adipocyte DNA methylation variations in human obesity. We discover extensive DNA methylation changes that are robustly associated with obesity (N = 190 samples, 691 loci in subcutaneous and 173 loci in visceral adipocytes, P < 1 × 10-7). We connect obesity-associated methylation variations to transcriptomic changes at >500 target genes, and identify putative methylation-transcription factor interactions. Through Mendelian Randomisation, we infer causal effects of methylation on obesity and obesity-induced metabolic disturbances at 59 independent loci. Targeted methylation sequencing, CRISPR-activation and gene silencing in adipocytes, further identifies regional methylation variations, underlying regulatory elements and novel cellular metabolic effects. Our results indicate DNA methylation is an important determinant of human obesity and its metabolic complications, and reveal mechanisms through which altered methylation may impact adipocyte functions.

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