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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Published in:Nature communications Vol. 11; no. 1; pp. 1465 - 13
Main Authors: 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.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 19.03.2020
Nature Publishing Group
Nature Portfolio
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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
Online Access:Get full text
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Summary: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.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-020-15291-z