Nutrigenetic Interaction of Spontaneously Hypertensive Rat Chromosome 20 Segment and High-Sucrose Diet Sensitizes to Metabolic Syndrome
Several corresponding regions of human and mammalian genomes have been shown to affect sensitivity to the manifestation of metabolic syndrome via nutrigenetic interactions. In this study, we assessed the effect of sucrose administration in a newly established congenic strain BN.SHR20, in which a lim...
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2022-08-01
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author | Ondřej Šeda Kristýna Junková Hana Malinska Adéla Kábelová Martina Hüttl Michaela Krupková Irena Markova František Liška Lucie Šedová |
author_facet | Ondřej Šeda Kristýna Junková Hana Malinska Adéla Kábelová Martina Hüttl Michaela Krupková Irena Markova František Liška Lucie Šedová |
author_sort | Ondřej Šeda |
collection | DOAJ |
description | Several corresponding regions of human and mammalian genomes have been shown to affect sensitivity to the manifestation of metabolic syndrome via nutrigenetic interactions. In this study, we assessed the effect of sucrose administration in a newly established congenic strain BN.SHR20, in which a limited segment of rat chromosome 20 from a metabolic syndrome model, spontaneously hypertensive rat (SHR), was introgressed into Brown Norway (BN) genomic background. We mapped the extent of the differential segment and compared the genomic sequences of BN vs. SHR within the segment in silico. The differential segment of SHR origin in BN.SHR20 spans about 9 Mb of the telomeric portion of the short arm of chromosome 20. We identified non-synonymous mutations e.g., in <i>ApoM</i>, <i>Notch4</i>, <i>Slc39a7</i>, <i>Smim29</i> genes and other variations in or near genes associated with metabolic syndrome in human genome-wide association studies. Male rats of BN and BN.SHR20 strains were fed a standard diet for 18 weeks (control groups) or 16 weeks of standard diet followed by 14 days of high-sucrose diet (HSD). We assessed the morphometric and metabolic profiles of all groups. Adiposity significantly increased only in BN.SHR20 after HSD. Fasting glycemia and the glucose levels during the oral glucose tolerance test were higher in BN.SHR20 than in BN groups, while insulin levels were comparable. The fasting levels of triacylglycerols were the highest in sucrose-fed BN.SHR20, both compared to the sucrose-fed BN and the control BN.SHR20. The non-esterified fatty acids and total cholesterol concentrations were higher in BN.SHR20 compared to their respective BN groups, and the HSD elicited an increase in non-esterified fatty acids only in BN.SHR20. In a new genetically defined model, we have isolated a limited genomic region involved in nutrigenetic sensitization to sucrose-induced metabolic disturbances. |
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spelling | doaj.art-6f82ef26a4d045d88546f670fd6a29962023-11-30T22:08:46ZengMDPI AGNutrients2072-66432022-08-011416342810.3390/nu14163428Nutrigenetic Interaction of Spontaneously Hypertensive Rat Chromosome 20 Segment and High-Sucrose Diet Sensitizes to Metabolic SyndromeOndřej Šeda0Kristýna Junková1Hana Malinska2Adéla Kábelová3Martina Hüttl4Michaela Krupková5Irena Markova6František Liška7Lucie Šedová8Institute of Biology and Medical Genetics, The First Faculty of Medicine, Charles University and the General University Hospital in Prague, 128 00 Prague, Czech RepublicInstitute of Biology and Medical Genetics, The First Faculty of Medicine, Charles University and the General University Hospital in Prague, 128 00 Prague, Czech RepublicCentre for Experimental Medicine, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech RepublicInstitute of Biology and Medical Genetics, The First Faculty of Medicine, Charles University and the General University Hospital in Prague, 128 00 Prague, Czech RepublicCentre for Experimental Medicine, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech RepublicInstitute of Biology and Medical Genetics, The First Faculty of Medicine, Charles University and the General University Hospital in Prague, 128 00 Prague, Czech RepublicCentre for Experimental Medicine, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech RepublicInstitute of Biology and Medical Genetics, The First Faculty of Medicine, Charles University and the General University Hospital in Prague, 128 00 Prague, Czech RepublicInstitute of Biology and Medical Genetics, The First Faculty of Medicine, Charles University and the General University Hospital in Prague, 128 00 Prague, Czech RepublicSeveral corresponding regions of human and mammalian genomes have been shown to affect sensitivity to the manifestation of metabolic syndrome via nutrigenetic interactions. In this study, we assessed the effect of sucrose administration in a newly established congenic strain BN.SHR20, in which a limited segment of rat chromosome 20 from a metabolic syndrome model, spontaneously hypertensive rat (SHR), was introgressed into Brown Norway (BN) genomic background. We mapped the extent of the differential segment and compared the genomic sequences of BN vs. SHR within the segment in silico. The differential segment of SHR origin in BN.SHR20 spans about 9 Mb of the telomeric portion of the short arm of chromosome 20. We identified non-synonymous mutations e.g., in <i>ApoM</i>, <i>Notch4</i>, <i>Slc39a7</i>, <i>Smim29</i> genes and other variations in or near genes associated with metabolic syndrome in human genome-wide association studies. Male rats of BN and BN.SHR20 strains were fed a standard diet for 18 weeks (control groups) or 16 weeks of standard diet followed by 14 days of high-sucrose diet (HSD). We assessed the morphometric and metabolic profiles of all groups. Adiposity significantly increased only in BN.SHR20 after HSD. Fasting glycemia and the glucose levels during the oral glucose tolerance test were higher in BN.SHR20 than in BN groups, while insulin levels were comparable. The fasting levels of triacylglycerols were the highest in sucrose-fed BN.SHR20, both compared to the sucrose-fed BN and the control BN.SHR20. The non-esterified fatty acids and total cholesterol concentrations were higher in BN.SHR20 compared to their respective BN groups, and the HSD elicited an increase in non-esterified fatty acids only in BN.SHR20. In a new genetically defined model, we have isolated a limited genomic region involved in nutrigenetic sensitization to sucrose-induced metabolic disturbances.https://www.mdpi.com/2072-6643/14/16/3428metabolic syndromecongenic ratanimal modelnutrigenetics |
spellingShingle | Ondřej Šeda Kristýna Junková Hana Malinska Adéla Kábelová Martina Hüttl Michaela Krupková Irena Markova František Liška Lucie Šedová Nutrigenetic Interaction of Spontaneously Hypertensive Rat Chromosome 20 Segment and High-Sucrose Diet Sensitizes to Metabolic Syndrome Nutrients metabolic syndrome congenic rat animal model nutrigenetics |
title | Nutrigenetic Interaction of Spontaneously Hypertensive Rat Chromosome 20 Segment and High-Sucrose Diet Sensitizes to Metabolic Syndrome |
title_full | Nutrigenetic Interaction of Spontaneously Hypertensive Rat Chromosome 20 Segment and High-Sucrose Diet Sensitizes to Metabolic Syndrome |
title_fullStr | Nutrigenetic Interaction of Spontaneously Hypertensive Rat Chromosome 20 Segment and High-Sucrose Diet Sensitizes to Metabolic Syndrome |
title_full_unstemmed | Nutrigenetic Interaction of Spontaneously Hypertensive Rat Chromosome 20 Segment and High-Sucrose Diet Sensitizes to Metabolic Syndrome |
title_short | Nutrigenetic Interaction of Spontaneously Hypertensive Rat Chromosome 20 Segment and High-Sucrose Diet Sensitizes to Metabolic Syndrome |
title_sort | nutrigenetic interaction of spontaneously hypertensive rat chromosome 20 segment and high sucrose diet sensitizes to metabolic syndrome |
topic | metabolic syndrome congenic rat animal model nutrigenetics |
url | https://www.mdpi.com/2072-6643/14/16/3428 |
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