FAM13A affects body fat distribution and adipocyte function
| Autor: | Joshua W. Knowles, Xiang Zhou, Stephen B. Montgomery, Tracey McLaughlin, Myung K. Shin, Mohsen Fathzadeh, Dermot F. Reilly, Panjamaporn Sangwung, Marcus M. Seldin, Mark P. Keller, Thomas Quertermous, Yuko Tada, Indumathi Chennamsetty, Aldons J. Lusis, Jing Yang, Cliona Molony, Michael J. Gloudemans, Martin Wabitsch, Erik Ingelsson, Ivan Carcamo-Orive, Naomi L. Cook, Jiehan Li, Gerald M. Reaven, Allan Attie, Abhiram Rao |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male medicine.medical_treatment Messenger General Physics and Astronomy Adipose tissue Inbred C57BL chemistry.chemical_compound Mice 0302 clinical medicine Adipocyte Adipocytes Body Fat Distribution 2.1 Biological and endogenous factors Aetiology lcsh:Science Mice Knockout Gene knockdown Multidisciplinary Adipogenesis GTPase-Activating Proteins Diabetes Cell Differentiation Single Nucleotide Phenotype Gene expression profiling Gene Knockdown Techniques Medical Genetics medicine.medical_specialty Science Knockout 1.1 Normal biological development and functioning Subcutaneous Fat Biology Intra-Abdominal Fat Polymorphism Single Nucleotide Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Underpinning research Internal medicine medicine Genetics Animals Humans Metabolomics RNA Messenger Obesity Allele Polymorphism Metabolic and endocrine Genetic association study Nutrition Medicinsk genetik Insulin Prevention Human Genome Metabolic diseases General Chemistry medicine.disease Mice Inbred C57BL 030104 developmental biology Endocrinology HEK293 Cells chemistry Genetic Loci RNA lcsh:Q Insulin Resistance 030217 neurology & neurosurgery Genome-Wide Association Study |
| Zdroj: | Nature communications, vol 11, iss 1 Nature Communications, Vol 11, Iss 1, Pp 1-13 (2020) Nature Communications |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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