A Weingarten1, L Turchetti2, K Krohn3, I Klöting4, M Kern1,5, P Kovacs1, M Stumvoll1,2, M Blüher1,2, N Klöting1. 1. IFB AdiposityDiseases, University of Leipzig, Leipzig, Germany. 2. Department of Medicine, University of Leipzig, Leipzig, Germany. 3. Core Unit IZKF, University of Leipzig, Leipzig, Germany. 4. Laboratory Animal Science, University of Greifswald, Karlsburg, Germany. 5. German Center for Diabetes Research (DZD), Leipzig, Germany.
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.
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.
Authors: Nora Klöting; Timothy E Graham; Janin Berndt; Susan Kralisch; Peter Kovacs; Christopher J Wason; Mathias Fasshauer; Michael R Schön; Michael Stumvoll; Matthias Blüher; Barbara B Kahn Journal: Cell Metab Date: 2007-07 Impact factor: 27.287
Authors: Tomasz Stokowy; Markus Eszlinger; Michał Świerniak; Krzysztof Fujarewicz; Barbara Jarząb; Ralf Paschke; Knut Krohn Journal: BMC Res Notes Date: 2014-03-13
Authors: Mari T Kaartinen; Mansi Arora; Sini Heinonen; Aila Rissanen; Jaakko Kaprio; Kirsi H Pietiläinen Journal: Int J Mol Sci Date: 2020-11-05 Impact factor: 5.923