FAM13A affects body fat distribution and adipocyte function

Mohsen Fathzadeh; Jiehan Li; Abhiram Rao; Naomi Cook; Indumathi Chennamsetty; Marcus Seldin; Xiang Zhou; Panjamaporn Sangwung; Michael J. Gloudemans; Mark Keller; Allan Attie; Jing Yang; Martin Wabitsch; Ivan Carcamo-Orive; Yuko Tada; Aldons J. Lusis; Myung Kyun Shin; Cliona M. Molony; Tracey McLaughlin; Gerald Reaven; Stephen B. Montgomery; Dermot Reilly; Thomas Quertermous; Erik Ingelsson; Joshua W. Knowles

doi:10.1038/s41467-020-15291-z

FAM13A affects body fat distribution and adipocyte function

Mohsen Fathzadeh, Jiehan Li, Abhiram Rao, Naomi Cook, Indumathi Chennamsetty, Marcus Seldin, Xiang Zhou, Panjamaporn Sangwung, Michael J. Gloudemans, Mark Keller, Allan Attie, Jing Yang, Martin Wabitsch, Ivan Carcamo-Orive, Yuko Tada, Aldons J. Lusis, Myung Kyun Shin, Cliona M. Molony, Tracey McLaughlin, Gerald ReavenStephen B. Montgomery, Dermot Reilly, Thomas Quertermous, Erik Ingelsson, Joshua W. Knowles

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Article number	1465
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-15291-z
State	Published - Dec 1 2020

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/s41467-020-15291-z

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Fathzadeh, M., Li, J., Rao, A., Cook, N., Chennamsetty, I., Seldin, M., Zhou, X., Sangwung, P., Gloudemans, M. J., Keller, M., Attie, A., Yang, J., Wabitsch, M., Carcamo-Orive, I., Tada, Y., Lusis, A. J., Shin, M. K., Molony, C. M., McLaughlin, T., ... Knowles, J. W. (2020). FAM13A affects body fat distribution and adipocyte function. Nature communications, 11(1), Article 1465. https://doi.org/10.1038/s41467-020-15291-z

Fathzadeh, M, Li, J, Rao, A, Cook, N, Chennamsetty, I, Seldin, M, Zhou, X, Sangwung, P, Gloudemans, MJ, Keller, M, Attie, A, Yang, J, Wabitsch, M, Carcamo-Orive, I, Tada, Y, Lusis, AJ, Shin, MK, Molony, CM, McLaughlin, T, Reaven, G, Montgomery, SB, Reilly, D, Quertermous, T, Ingelsson, E & Knowles, JW 2020, 'FAM13A affects body fat distribution and adipocyte function', Nature communications, vol. 11, no. 1, 1465. https://doi.org/10.1038/s41467-020-15291-z

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abstract = "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.",

author = "Mohsen Fathzadeh and Jiehan Li and Abhiram Rao and Naomi Cook and Indumathi Chennamsetty and Marcus Seldin and Xiang Zhou and Panjamaporn Sangwung and Gloudemans, {Michael J.} and Mark Keller and Allan Attie and Jing Yang and Martin Wabitsch and Ivan Carcamo-Orive and Yuko Tada and Lusis, {Aldons J.} and Shin, {Myung Kyun} and Molony, {Cliona M.} and Tracey McLaughlin and Gerald Reaven and Montgomery, {Stephen B.} and Dermot Reilly and Thomas Quertermous and Erik Ingelsson and Knowles, {Joshua W.}",

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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.

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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FAM13A affects body fat distribution and adipocyte function

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