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dc.contributor.authorKulyté, Agné
dc.contributor.authorLundbäck, Veroniqa
dc.contributor.authorLindgren, Cecilia M
dc.contributor.authorLuan, Jian'an
dc.contributor.authorLotta, Luca A
dc.contributor.authorLangenberg, Claudia
dc.contributor.authorArner, Peter
dc.contributor.authorStrawbridge, Rona J
dc.contributor.authorDahlman, Ingrid
dc.date.accessioned2020-04-18T02:55:14Z
dc.date.available2020-04-18T02:55:14Z
dc.date.issued2020-01-25
dc.identifier.issn2212-8778
dc.identifier.otherPMC7021539
dc.identifier.other32180562
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/304511
dc.description.abstractOBJECTIVES: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.
dc.languageeng
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 2212-8778
dc.sourcenlmid: 101605730
dc.subjectAdipocytes
dc.subjectGene Expression
dc.subjectSubcutaneous
dc.subjectGenetic Variants
dc.subjectLipolysis
dc.titleGenome-wide association study of adipocyte lipolysis in the GENetics of adipocyte lipolysis (GENiAL) cohort.
dc.typeArticle
dc.date.updated2020-04-18T02:55:14Z
prism.endingPage96
prism.publicationNameMolecular metabolism
prism.startingPage85
prism.volume34
dc.identifier.doi10.17863/CAM.51590
rioxxterms.versionofrecord10.1016/j.molmet.2020.01.009
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International