Journal article
Genome-wide association study of adipocyte lipolysis in the GENetics of adipocyte lipolysis (GENiAL) cohort
- Abstract:
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Objectives
Lipolysis, hydrolysis of triglycerides to fatty acids in adipocytes, is tightly regulated, poorly understood, and, if perturbed, can lead to metabolic diseases including obesity and type 2 diabetes. The goal of this study was to identify the genetic regulators of lipolysis and elucidate their molecular mechanisms.
Methods
Adipocytes from abdominal subcutaneous adipose tissue biopsies were isolated and were incubated without (spontaneous lipolysis) or with a catecholamine (stimulated lipolysis) to analyze lipolysis. DNA was extracted and genome-wide genotyping and imputation conducted. After quality control, 939 samples with genetic and lipolysis data were available. Genome-wide association studies of spontaneous and stimulated lipolysis were conducted. Subsequent in vitro gene expression analyses were used to identify candidate genes and explore their regulation of adipose tissue biology.
Results
One locus on chromosome 19 demonstrated genome-wide significance with spontaneous lipolysis. 60 loci showed suggestive associations with spontaneous or stimulated lipolysis, of which many influenced both traits. In the chromosome 19 locus, only HIF3A was expressed in the adipocytes and displayed genotype-dependent gene expression. HIF3A knockdown in vitro increased lipolysis and the expression of key lipolysis-regulating genes.
Conclusions
In conclusion, we identified a genetic regulator of spontaneous lipolysis and provided evidence of HIF3A as a novel key regulator of lipolysis in subcutaneous adipocytes as the mechanism through which the locus influences adipose tissue biology.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Publisher copy:
- 10.1016/j.molmet.2020.01.009
Authors
- Publisher:
- Elsevier
- Journal:
- Molecular Metabolism More from this journal
- Volume:
- 34
- Issue:
- April 2020
- Pages:
- 85-96
- Publication date:
- 2020-01-25
- Acceptance date:
- 2020-01-15
- DOI:
- EISSN:
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2212-8778
- Pmid:
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32180562
- Language:
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English
- Keywords:
- Pubs id:
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1090206
- Local pid:
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pubs:1090206
- Deposit date:
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2020-08-27
Terms of use
- Copyright holder:
- Kulyté et al.
- Copyright date:
- 2020
- Rights statement:
- ©2020 The Author(s). Published by Elsevier GmbH. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
- Notes:
- A correction to this article is available at: 10.1016/j.molmet.2020.101072
- Licence:
- CC Attribution (CC BY)
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