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  The direction of cross affects [corrected] obesity after puberty in male but not female offspring

Kärst, S., Arends, D., Heise, S., Trost, J., Yaspo-Lehrach, M.-L., Amstislavskiy, V., et al. (2015). The direction of cross affects [corrected] obesity after puberty in male but not female offspring. BMC Genomics, 16, 904. doi:10.1186/s12864-015-2164-2.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-4368-7 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-4369-5
Genre: Journal Article

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art%3A10.1186%2Fs12864-015-2164-2.pdf (Publisher version), 940KB
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2015-05-01
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© 2015 Kärst et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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 Creators:
Kärst, Stefan1, Author
Arends, Danny1, Author
Heise, Sebastian1, Author
Trost, Jan1, Author
Yaspo-Lehrach, Marie-Laure2, Author              
Amstislavskiy, Vyacheslav3, Author              
Risch, Thomas2, Author
Lehrach, Hans4, Author              
Affiliations:
1Albrecht Daniel Thaer-Institut für Agrar- und Gartenbauwissenschaften, Humboldt-Universität zu Berlin, ou_persistent22              
2Gene Regulation and Systems Biology of Cancer (Marie-Laure Yaspo), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2117287              
3Human Chromosome 21 (Marie-Laure Yaspo), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479652              
4Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              

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Free keywords: Allele-specific gene expression Allelic imbalance High fat diet Imprinting Peg3 Circadian rhythm Sex differences Sex hormones
 Abstract: Background We investigated parent-of-origin and allele-specific expression effects on obesity and hepatic gene expression in reciprocal crosses between the Berlin Fat Mouse Inbred line (BFMI) and C57Bl/6NCrl (B6N). Results We found that F1-males with a BFMI mother developed 1.8 times more fat mass on a high fat diet at 10 weeks than F1-males of a BFMI father. The phenotype was detectable from six weeks on and was preserved after cross-fostering. RNA-seq data of liver provided evidence for higher biosynthesis and elongation of fatty acids (p = 0.00635) in obese male offspring of a BFMI mother versus lean offspring of a BFMI father. Furthermore, fatty acid degradation (p = 0.00198) and the peroxisome pathway were impaired (p = 0.00094). The circadian rhythm was affected as well (p = 0.00087). Among the highest up-regulated protein coding genes in obese males were Acot4 (1.82 fold, p = 0.022), Cyp4a10 (1.35 fold, p = 0.026) and Cyp4a14 (1.32 fold, p = 0.012), which hydroxylize fatty acids and which are known to be increased in liver steatosis. Obese males showed lower expression of the genetically imprinted and paternally expressed 3 (Peg3) gene (0.31 fold, p = 0.046) and higher expression of the androgen receptor (Ar) gene (2.38 fold, p = 0.068). Allelic imbalance was found for expression of ATP-binding cassette transporter gene Abca8b. Several of the differentially expressed genes contain estrogen response elements. Conclusions Parent-of-origin effects during gametogenesis and/or fetal development in an obese mother epigenetically modify the transcription of genes that lead to enhanced fatty acid synthesis and impair β-oxidation in the liver of male, but not female F1 offspring. Down-regulation of Peg3 could contribute to trigger this metabolic setting. At puberty, higher amounts of the androgen receptor and altered access to estrogen response elements in affected genes are likely responsible for male specific expression of genes that were epigenetically triggered. A suggestive lack of estrogen binding motifs was found for highly down-regulated genes in adult hepatocytes of obese F1 males (p = 0.074).

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Language(s): eng - English
 Dates: 2015-05-192015-10-292015-11-06
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1186/s12864-015-2164-2
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Title: BMC Genomics
Source Genre: Journal
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Publ. Info: BioMed Central
Pages: - Volume / Issue: 16 Sequence Number: - Start / End Page: 904 Identifier: ISSN: 1471-2164
CoNE: https://pure.mpg.de/cone/journals/resource/111000136905010