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Animal Models

Novel genes on rat chromosome 10 are linked to body fat mass, preadipocyte number and adipocyte size

International Journal of Obesity volume 40, pages 1832–1840 (2016)Cite this article

Subjects

Abstract

Background:

The genetic architecture of obesity is multifactorial. We have previously identified a quantitative trait locus (QTL) on rat chromosome 10 in a F2 cross of Wistar Ottawa Karlsburg (WOKW) and Dark Agouti (DA) rats responsible for obesity-related traits. The QTL was confirmed in congenic DA.WOKW10 rats. To pinpoint the region carrying causal genes, we established two new subcongenic lines, L1 and L2, with smaller refined segments of chromosome 10 to identify novel candidate genes.

Methods:

All lines were extensively characterized under different diet conditions. We employed transcriptome analysis in visceral adipose tissue (VAT) by RNA-Seq technology to identify potential underlying genes in the segregating regions. Three candidate genes were measured in human paired samples of VAT and subcutaneous (SC) AT (SAT) (N=304) individuals with a wide range of body weight and glucose homeostasis parameters.

Results:

DA.WOKW and L1 subcongenic lines were protected against body fat gain under high-fat diet (HFD), whereas L2 and DA had significantly more body fat after high-fat feeding. Interestingly, adipocyte size distribution in SAT and epigonadal AT of L1 subcongenic rats did not undergo typical ballooning under HFD and the number of preadipocytes in AT was significantly elevated in L2 compared with L1 and parental rats. Transcriptome analysis identified three candidate genes in VAT on rat chromosome 10. In humans, these candidate genes were differentially expressed between SAT and VAT. Moreover, HID1 mRNA significantly correlates with parameters of obesity and glucose metabolism.

Conclusions:

Our data suggest novel candidate genes for obesity that map on rat chromosome 10 in an interval 102.2–104.7 Mb and are strongly associated with body fat mass regulation, preadipocyte number and adipocyte size in rats. Among those genes, AT head involution defective (HID1) mRNA expression may be relevant for human fat distribution and glucose homeostasis.

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Acknowledgements

We thank Viola Döbel, Eva Böge, Manuela Thiemicke and Susan Berthold of University of Leipzig for technical assistance. This work was supported by the research group ‘SFB1052’, B1 (to MB) and B4 (to NK) funded by Deutsche Forschungsgemeinschaft, and by the Federal Ministry of Education and Research (BMBF), Germany, IFB AdiposityDiseases’ FKZ: 01EO1501 (to NK, AW and PK) and DZD (82DZD00601).

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Authors and Affiliations

  1. IFB AdiposityDiseases, University of Leipzig, Leipzig, Germany

    A Weingarten, M Kern, P Kovacs, M Stumvoll, M Blüher & N Klöting

  2. Department of Medicine, University of Leipzig, Leipzig, Germany

    L Turchetti, M Stumvoll & M Blüher

  3. Core Unit IZKF, University of Leipzig, Leipzig, Germany

    K Krohn

  4. Laboratory Animal Science, University of Greifswald, Karlsburg, Germany

    I Klöting

  5. German Center for Diabetes Research (DZD), Leipzig, Germany

    M Kern

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  1. A Weingarten
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Correspondence to N Klöting.

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The authors declare no conflict of interest.

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Author contributions

NK conceived the research ideas, supervised the project and wrote manuscript. AW researched data and wrote manuscript. IK and MB reviewed/edited the manuscript. MK performed human adipose tissue expression analysis. PK reviewed manuscript and contributed to discussion. MS conceived the research ideas and reviewed/edited the manuscript. NK is the guarantor of this work, had full access to all data in the study and takes responsibility for the integrity of the data and data analysis.

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Weingarten, A., Turchetti, L., Krohn, K. et al. Novel genes on rat chromosome 10 are linked to body fat mass, preadipocyte number and adipocyte size. Int J Obes 40, 1832–1840 (2016). https://doi.org/10.1038/ijo.2016.127

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