TY - JOUR
T1 - FAM13A affects body fat distribution and adipocyte function
AU - Fathzadeh, Mohsen
AU - Li, Jiehan
AU - Rao, Abhiram
AU - Cook, Naomi
AU - Chennamsetty, Indumathi
AU - Seldin, Marcus
AU - Zhou, Xiang
AU - Sangwung, Panjamaporn
AU - Gloudemans, Michael J.
AU - Keller, Mark
AU - Attie, Allan
AU - Yang, Jing
AU - Wabitsch, Martin
AU - Carcamo-Orive, Ivan
AU - Tada, Yuko
AU - Lusis, Aldons J.
AU - Shin, Myung Kyun
AU - Molony, Cliona M.
AU - McLaughlin, Tracey
AU - Reaven, Gerald
AU - Montgomery, Stephen B.
AU - Reilly, Dermot
AU - Quertermous, Thomas
AU - Ingelsson, Erik
AU - Knowles, Joshua W.
N1 - Funding Information:
This study was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK107437 and 1R01DK106236), the Stanford Diabetes Research Center (NIDDK award P30DK116074), and an unrestricted grant from Merck. We would like to thank Casimiro Castillejo-Lopez and Ewa Bielczyk-Maczyńska for constructing plasmids and sharing experimental protocols, respectively.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-020-15291-z
DO - 10.1038/s41467-020-15291-z
M3 - Article
C2 - 32193374
AN - SCOPUS:85082064549
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1465
ER -