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Regulatory variants at KLF14 influence type 2 diabetes risk via a female-specific effect on adipocyte size and body composition

文献类型：期刊论文

作者Small, Kerrin S.2; Glastonbury, Craig A.2; Quaye, Lydia2; Vinuela, Ana2; Tsai, Pei-Chien2; Nag, Abhishek2; Bell, Jordana T.2; Todorcevic, Marijana3; Horikoshi, Momoko3,8; Neville, Matt J.3
刊名NATURE GENETICS
出版日期2018
卷号50期号:4页码:572-+
关键词Cellular heterogeneity DNA methylation EWAS
ISSN号1061-4036
DOI10.1038/s41588-018-0088-x
文献子类Article
英文摘要Individual risk of type 2 diabetes (T2D) is modified by perturbations to the mass, distribution and function of adipose tissue. To investigate the mechanisms underlying these associations, we explored the molecular, cellular and whole-body effects of T2D-associated alleles near KLF14. We show that KLF14 diabetes-risk alleles act in adipose tissue to reduce KLF14 expression and modulate, in trans, the expression of 385 genes. We demonstrate, in human cellular studies, that reduced KLF14 expression increases pre-adipocyte proliferation but disrupts lipogenesis, and in mice, that adipose tissue-specific deletion of Klf14 partially recapitulates the human phenotype of insulin resistance, dyslipidemia and T2D. We show that carriers of the KLF14 T2D risk allele shift body fat from gynoid stores to abdominal stores and display a marked increase in adipocyte cell size, and that these effects on fat distribution, and the T2D association, are female specific. The metabolic risk associated with variation at this imprinted locus depends on the sex both of the subject and of the parent from whom the risk allele derives.
学科主题Genetics & Heredity
WOS关键词SCALE ASSOCIATION ANALYSIS ; ADIPOSE GENE-EXPRESSION ; INSULIN-RESISTANCE ; DNA METHYLATION ; TRANSCRIPTION FACTORS ; FAT DISTRIBUTION ; MESSENGER-RNA ; LOCI ; IDENTIFICATION ; OBESITY
语种英语
WOS记录号WOS:000429529300017
出版者NATURE PUBLISHING GROUP
版本出版稿
源URL[http://202.127.25.144/handle/331004/709]  
专题中国科学院上海生命科学研究院营养科学研究所
作者单位1.DeCODE Genet, Reykjavik, Iceland;
2.Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England;
3.Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England;
4.Univ Virginia, Dept Biomed Engn, Ctr Publ Hlth Genom, Charlottesville, VA USA;
5.Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA;
6.Univ Penn, Perelman Sch Med, Dept Genet, Cardiovasc Inst,Dept Med, Philadelphia, PA 19104 USA;
7.MRC, Harwell Inst, Biocomp, Oxford, England;
8.Univ Oxford, Wellcome Ctr Human Genet, Oxford, England;
9.MRC, Harwell Inst, Genet Type Diabet 2, Oxford, England;
10.Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford, England;
推荐引用方式
GB/T 7714		 Small, Kerrin S.,Glastonbury, Craig A.,Quaye, Lydia,et al. Regulatory variants at KLF14 influence type 2 diabetes risk via a female-specific effect on adipocyte size and body composition[J]. NATURE GENETICS,2018,50(4):572-+.
APA Small, Kerrin S..,Glastonbury, Craig A..,Quaye, Lydia.,Vinuela, Ana.,Tsai, Pei-Chien.,...&,.(2018).Regulatory variants at KLF14 influence type 2 diabetes risk via a female-specific effect on adipocyte size and body composition.NATURE GENETICS,50(4),572-+.
MLA Small, Kerrin S.,et al."Regulatory variants at KLF14 influence type 2 diabetes risk via a female-specific effect on adipocyte size and body composition".NATURE GENETICS 50.4(2018):572-+.

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来源：上海营养与健康研究所

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