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Research Article

A Stratified Transcriptomics Analysis of Polygenic Fat and Lean Mouse Adipose Tissues Identifies Novel Candidate Obesity Genes

  • Nicholas M. Morton mail,

    nik.morton@ed.ac.uk

    Affiliation: Molecular Metabolism Group, BHF/University Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, United Kingdom

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  • Yvonne B. Nelson,

    Affiliation: Molecular Metabolism Group, BHF/University Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, United Kingdom

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  • Zoi Michailidou,

    Affiliation: Tissue Remodelling and Regeneration Group, Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh, United Kingdom

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  • Emma M. Di Rollo,

    Affiliation: Molecular Metabolism Group, BHF/University Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, United Kingdom

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  • Lynne Ramage,

    Affiliation: Molecular Metabolism Group, BHF/University Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, United Kingdom

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  • Patrick W. F. Hadoke,

    Affiliation: Endocrinology Unit, BHF/University Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, United Kingdom

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  • Jonathan R. Seckl,

    Affiliation: Endocrinology Unit, BHF/University Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, United Kingdom

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  • Lutz Bunger,

    Affiliation: Animal Breeding and Development Team, Sustainable Livestock Systems, SAC, Bush Estate, Penicuik, United Kingdom

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  • Simon Horvat,

    Affiliation: Animal Science Department, Biotechnical Faculty, University of Ljubljana, and National Institute of Chemistry, Hajdrihova, Ljubljana, Slovenia

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  • Christopher J. Kenyon,

    Affiliation: Endocrinology Unit, BHF/University Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, United Kingdom

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  • Donald R. Dunbar

    Affiliation: Bioinformatics Core, BHF/University Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, United Kingdom

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  • Published: September 07, 2011
  • DOI: 10.1371/journal.pone.0023944

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Author Summary:

Posted by NikMorton on 08 Sep 2011 at 21:43 GMT

Genetic effects can explain between 50-80% of the fatness in the normal population. Loci identified through classical genetics and genome-wide association studies (GWAS) in humans highlighted the importance of brain regulated energy balance but have accounted for a disappointingly small proportion of this genetic legacy (~10%). Investigating defined animal obesity models offers one powerful way of identifying novel obesity loci. Since GWAS have also revealed that genes involved in fat cell function contribute to obesity, we searched for adipose tissue-specific candidate obesity genes in a unique polygenic mouse model selected over many generations for divergent fatness. Gene candidates were enriched by comparing their expression patterns in adipose tissues to other organs, combined with known information on the gene and fatness inheritance patterns. We successfully linked some of the candidate genes with fat cell function. We also gained new mechanistic insights into related gene responses in adipose tissue when we exposed the mice to fatty diets. Our results place adipose tissue mechanisms in the frame as an important genetic contributor to obesity, improve our understanding of altered fat cell biology in this state and reveal potential new therapeutic targets.

Competing interests declared: I am the lead author of the work. I am supplying a short author summary of the article only. NMM