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  (Epi)genetic regulation of CRTC1 in human eating behaviour and fat distribution

Rohde, K., Keller, M., la Cour Poulsen, L., Rønningen, T., Stumvoll, M., Tönjes, A., et al. (2019). (Epi)genetic regulation of CRTC1 in human eating behaviour and fat distribution. EBioMedicine, 44, 476-488. doi:10.1016/j.ebiom.2019.05.050.

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Item Permalink: https://hdl.handle.net/21.11116/0000-0003-BE9C-8 Version Permalink: https://hdl.handle.net/21.11116/0000-0004-4048-3
Genre: Journal Article

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 Creators:
Rohde, Kerstin1, 2, 3, Author
Keller, Maria3, Author
la Cour Poulsen, Lars2, Author
Rønningen, Torunn2, Author
Stumvoll, Michael4, Author
Tönjes, Anke4, Author
Kovacs, Peter3, Author
Horstmann, Annette5, Author           
Villringer, Arno5, 6, Author           
Blüher, Matthias3, 4, Author
Böttcher, Yvonne1, 2, 3, Author
Affiliations:
1Institute of Clinical Medicine, University of Oslo, Norway, ou_persistent22              
2Department of Clinical Molecular Biology, Akershus University Hospital, Lørenskog, Norway, ou_persistent22              
3Integrated Research and Treatment Center Adiposity Diseases, University of Leipzig, Germany, ou_persistent22              
4Faculty of Medicine, University of Leipzig, Germany, ou_persistent22              
5Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, Leipzig, DE, ou_634549              
6Clinic for Cognitive Neurology, University of Leipzig, Germany, ou_persistent22              

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Free keywords: CRTC1; rs7256986; DNA methylation; Fat distribution; Eating behaviour
 Abstract: Background

In brain, CREB-regulated transcription co-activator 1 (CRTC1) is involved in metabolic dysregulation. In humans a SNP in CRTC1 was associated to body fat percentage and two SNPs affected RNA Pol II binding and chromatin structure, implying epigenetic regulation of CRTC1. We sought to understand the relevance of CRTC1 SNPs, DNA methylation and expression in human eating behaviour and its relationship to clinical variables of obesity in blood and adipose tissue.
Methods

13 CRTC1 SNPs were included to analyze eating behaviour. For rs7256986, follow up association analyses were applied on DNA methylation, CRTC1 expression and clinical parameters. Linear regression was used throughout the study adjusted for age, sex and BMI. Besides data extraction from previous work, rs7256986 was de-novo genotyped and DNA methylation was evaluated by using pyrosequencing.
Findings

We found several SNPs in the CRTC1 locus nominally associated with human eating behaviour or 2hr postprandial insulin levels and observed a correlation with alcohol and coffee intake (all P < 0.05). G-allele carriers of rs7256986 showed slightly increased hip circumference. We showed that rs7256986 represents a methylation quantitative trait locus (meQTL) in whole blood and adipose tissue. The presence of the SNP and/or DNA methylation correlated with CRTC1 gene expression which in turn, related to BMI and fat distribution.
Interpretation

Our data support the known role of CRCT1 regulating energy metabolism in brain. Here, we highlight relevance of CRTC1 regulation in blood and adipose tissue.

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Language(s): eng - English
 Dates: 2019-05-142019-04-162019-05-242019-05-30
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.ebiom.2019.05.050
Other: Epub 2019
PMID: 31153815
 Degree: -

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Project name : -
Grant ID : 01EO1501
Funding program : -
Funding organization : IFB Adiposity Diseases, German Federal Ministry of Education and Research (BMBF)
Project name : International Postdoctoral Fellowship Programme / SCIENTIA-FELLOWS
Grant ID : 609020
Funding program : Funding Programme 7
Funding organization : European Commission (EC)
Project name : -
Grant ID : -
Funding program : -
Funding organization : South Eastern Norway Regional Health Authority, Norway
Project name : -
Grant ID : 01GI1128
Funding program : -
Funding organization : Kompetenznetz Adipositas, German Federal Ministry of Education and Research (BMBF)
Project name : Obesity Mechanisms / SFB 1052
Grant ID : -
Funding program : -
Funding organization : Deutsche Forschungsgemeinschaft (DFG)
Project name : -
Grant ID : -
Funding program : -
Funding organization : German Diabetes Association

Source 1

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Title: EBioMedicine
Source Genre: Journal
 Creator(s):
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Publ. Info: Amsterdam : Elsevier
Pages: - Volume / Issue: 44 Sequence Number: - Start / End Page: 476 - 488 Identifier: ISSN: 2352-3964
CoNE: https://pure.mpg.de/cone/journals/resource/2352-3964