FAM13A affects body fat distribution and adipocyte function

Genetic variation in the FAM13A (Family with Sequence Similarity 13 Member A) locus has been associated with several glycemic and metabolic traits in genome-wide association studies (GWAS). Here, we demonstrate that in humans, FAM13A alleles are associated with increased FAM13A expression in subcuta...

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Vydáno v:	Nature communications Ročník 11; číslo 1; s. 1465 - 13
Hlavní autoři:	Fathzadeh, Mohsen, Li, Jiehan, Rao, Abhiram, Cook, Naomi, Chennamsetty, Indumathi, Seldin, Marcus, Zhou, Xiang, Sangwung, Panjamaporn, Gloudemans, Michael J., Keller, Mark, Attie, Allan, Yang, Jing, Wabitsch, Martin, Carcamo-Orive, Ivan, Tada, Yuko, Lusis, Aldons J., Shin, Myung Kyun, Molony, Cliona M., McLaughlin, Tracey, Reaven, Gerald, Montgomery, Stephen B., Reilly, Dermot, Quertermous, Thomas, Ingelsson, Erik, Knowles, Joshua W.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 19.03.2020 Nature Publishing Group Nature Portfolio
Témata:	13/106 13/51 13/89 49/105 49/39 631/208/191/2018 631/208/205 631/443/319/1642 64/60 692/163/2743/393 82/1 96/1 Adipocytes Adipocytes - metabolism Adipogenesis - genetics Adipose tissue Animals Anthropometry Body fat Body Fat Distribution Cell Differentiation - genetics Differentiation Gene Knockdown Techniques Gene mapping Genetic diversity Genetic Loci Genetic variance Genome-wide association studies Genome-Wide Association Study GTPase-Activating Proteins - genetics GTPase-Activating Proteins - metabolism HEK293 Cells High fat diet Hip Humanities and Social Sciences Humans In vivo methods and tests Insulin Insulin resistance Insulin Resistance - genetics Intra-Abdominal Fat - metabolism Loci Male Mapping Metabolism Metabolomics Mice, Inbred C57BL Mice, Knockout multidisciplinary Phenotype Phenotypes Polymorphism, Single Nucleotide - genetics Preadipocytes RNA, Messenger - genetics RNA, Messenger - metabolism Science Science (multidisciplinary) Size distribution Subcutaneous Fat - metabolism
ISSN:	2041-1723, 2041-1723
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Shrnutí:	Genetic variation in the FAM13A (Family with Sequence Similarity 13 Member A) locus has been associated with several glycemic and metabolic traits in genome-wide association studies (GWAS). Here, we demonstrate that in humans, FAM13A alleles are associated with increased FAM13A expression in subcutaneous adipose tissue (SAT) and an insulin resistance-related phenotype (e.g. higher waist-to-hip ratio and fasting insulin levels, but lower body fat). In human adipocyte models, knockdown of FAM13A in preadipocytes accelerates adipocyte differentiation. In mice, Fam13a knockout (KO) have a lower visceral to subcutaneous fat (VAT/SAT) ratio after high-fat diet challenge, in comparison to their wild-type counterparts. Subcutaneous adipocytes in KO mice show a size distribution shift toward an increased number of smaller adipocytes, along with an improved adipogenic potential. Our results indicate that GWAS-associated variants within the FAM13A locus alter adipose FAM13A expression, which in turn, regulates adipocyte differentiation and contribute to changes in body fat distribution. Genetic variants in the FAM13A locus have been associated with anthropometric and glycemic traits. Here, using fine-mapping, in vitro knockdown studies in pre-adipocytes and in vivo knockout in mice, the authors show that FAM13A is involved in regulating fat distribution and metabolic traits.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-020-15291-z