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ATR-FTIR spectroscopy reveals genomic loci regulating the tissue response in high fat diet fed BXD recombinant inbred mouse strains.

Dogan A, Lasch P, Neuschl C, Millrose MK, Alberts R, Schughart K, Naumann D, Brockmann GA - BMC Genomics (2013)

Bottom Line: Obesity-associated organ-specific pathological states can be ensued from the dysregulation of the functions of the adipose tissues, liver and muscle.The analysis of genotype-phenotype correlations revealed significant quantitative trait loci (QTL) on chromosome 12 for the content of fat and collagen, collagen integrity, and the lipid to protein ratio in adipose tissue and on chromosome 17 for lipid to protein ratio in liver.The candidate genes in the QTL regions may contribute to obesity-related diseases in humans, in particular if the results can be verified in a bigger BXD cohort.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department for Crop and Animal Sciences, Humboldt-Universität zu Berlin, Invalidenstraße 42, 10115, Berlin, Germany.

ABSTRACT

Background: Obesity-associated organ-specific pathological states can be ensued from the dysregulation of the functions of the adipose tissues, liver and muscle. However, the influence of genetic differences underlying gross-compositional differences in these tissues is largely unknown. In the present study, the analytical method of ATR-FTIR spectroscopy has been combined with a genetic approach to identify genetic differences responsible for phenotypic alterations in adipose, liver and muscle tissues.

Results: Mice from 29 BXD recombinant inbred mouse strains were put on high fat diet and gross-compositional changes in adipose, liver and muscle tissues were measured by ATR-FTIR spectroscopy. The analysis of genotype-phenotype correlations revealed significant quantitative trait loci (QTL) on chromosome 12 for the content of fat and collagen, collagen integrity, and the lipid to protein ratio in adipose tissue and on chromosome 17 for lipid to protein ratio in liver. Using gene expression and sequence information, we suggest Rsad2 (viperin) and Colec11 (collectin-11) on chromosome 12 as potential quantitative trait candidate genes. Rsad2 may act as a modulator of lipid droplet contents and lipid biosynthesis; Colec11 might play a role in apoptopic cell clearance and maintenance of adipose tissue. An increased level of Rsad2 transcripts in adipose tissue of DBA/2J compared to C57BL/6J mice suggests a cis-acting genetic variant leading to differential gene activation.

Conclusion: The results demonstrate that the analytical method of ATR-FTIR spectroscopy effectively contributed to decompose the macromolecular composition of tissues that accumulate fat and to link this information with genetic determinants. The candidate genes in the QTL regions may contribute to obesity-related diseases in humans, in particular if the results can be verified in a bigger BXD cohort.

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Relative mRNA expression of 20 weeks old males on high fat diet. Relative mRNA expression level of Rsad2 from epididymal adipose tissue. Different BXD RI strains carrying either the C57BL/6J (B6) or DBA/2J (D2) allele at the position of the target gene were chosen randomly from the BXD recombinant inbred strains (one animal per strain) for gene expression analyses. Bar graphs with different letters are significantly different to a level of significance of p = 0.03; n = 6–8. Statistics were performed using the two-tailed Student’s t-test and bar graphs are mean values plus SD.
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Figure 4: Relative mRNA expression of 20 weeks old males on high fat diet. Relative mRNA expression level of Rsad2 from epididymal adipose tissue. Different BXD RI strains carrying either the C57BL/6J (B6) or DBA/2J (D2) allele at the position of the target gene were chosen randomly from the BXD recombinant inbred strains (one animal per strain) for gene expression analyses. Bar graphs with different letters are significantly different to a level of significance of p = 0.03; n = 6–8. Statistics were performed using the two-tailed Student’s t-test and bar graphs are mean values plus SD.

Mentions: Evidence for cis-regulation comes from genetic variation between B6 and D2 and expression QTLs (eQTL) for Rsad2 and Colec11 in segregating F2-populations. For example, for both genes, eQTLs were described for adipose tissues in the cross CastXC57BL6/J (CastB6/B6Cast F2), and in addition for Colec11 in the cross C3H/JxC57BL6/J (BH/HB F2) (GeneNetwork references: Probeset 10018174238 for Rsad2 in adipose tissue of cross CastB6/B6CAST F2, Database: UCLA CTB6/B6CTF2 Adipose (2005) mlratio; Probeset 10024397101 for Colec11 in adipose tissue of cross CastB6/B6CAST F2, Database: UCLA CTB6/B6CTF2 Adipose (2005) mlratio; Probeset 10024397101 for Colec11 in adipose tissue of cross BH/HBF2, Database: UCLA BHHBF2 Adipose (2005) mlratio). Because four out of 10 synonymous SNPs in the coding region of Rsad2 that exist between B6 and D2 also occur between Cast/J and B6 mice, it is very likely that the genetic variation in this gene could be responsible for expression or functional differences in both reference populations. The measurement of transcript amounts of Rsad2 and Colec11 in our high fat diet fed BXD RI strains carrying the alternative B6 and D2 alleles of the respective genes revealed 1.4 times higher mRNA amounts of Rsad2 of D2 carriers (p=0.03), while no expression difference was found for Colec11 (p=0.10) (Figure 4). These results suggest cis-acting genetic variation that interacts with environmental changes on the cellular level leading to differential gene activation of Rsad2 under different diets.


ATR-FTIR spectroscopy reveals genomic loci regulating the tissue response in high fat diet fed BXD recombinant inbred mouse strains.

Dogan A, Lasch P, Neuschl C, Millrose MK, Alberts R, Schughart K, Naumann D, Brockmann GA - BMC Genomics (2013)

Relative mRNA expression of 20 weeks old males on high fat diet. Relative mRNA expression level of Rsad2 from epididymal adipose tissue. Different BXD RI strains carrying either the C57BL/6J (B6) or DBA/2J (D2) allele at the position of the target gene were chosen randomly from the BXD recombinant inbred strains (one animal per strain) for gene expression analyses. Bar graphs with different letters are significantly different to a level of significance of p = 0.03; n = 6–8. Statistics were performed using the two-tailed Student’s t-test and bar graphs are mean values plus SD.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3717084&req=5

Figure 4: Relative mRNA expression of 20 weeks old males on high fat diet. Relative mRNA expression level of Rsad2 from epididymal adipose tissue. Different BXD RI strains carrying either the C57BL/6J (B6) or DBA/2J (D2) allele at the position of the target gene were chosen randomly from the BXD recombinant inbred strains (one animal per strain) for gene expression analyses. Bar graphs with different letters are significantly different to a level of significance of p = 0.03; n = 6–8. Statistics were performed using the two-tailed Student’s t-test and bar graphs are mean values plus SD.
Mentions: Evidence for cis-regulation comes from genetic variation between B6 and D2 and expression QTLs (eQTL) for Rsad2 and Colec11 in segregating F2-populations. For example, for both genes, eQTLs were described for adipose tissues in the cross CastXC57BL6/J (CastB6/B6Cast F2), and in addition for Colec11 in the cross C3H/JxC57BL6/J (BH/HB F2) (GeneNetwork references: Probeset 10018174238 for Rsad2 in adipose tissue of cross CastB6/B6CAST F2, Database: UCLA CTB6/B6CTF2 Adipose (2005) mlratio; Probeset 10024397101 for Colec11 in adipose tissue of cross CastB6/B6CAST F2, Database: UCLA CTB6/B6CTF2 Adipose (2005) mlratio; Probeset 10024397101 for Colec11 in adipose tissue of cross BH/HBF2, Database: UCLA BHHBF2 Adipose (2005) mlratio). Because four out of 10 synonymous SNPs in the coding region of Rsad2 that exist between B6 and D2 also occur between Cast/J and B6 mice, it is very likely that the genetic variation in this gene could be responsible for expression or functional differences in both reference populations. The measurement of transcript amounts of Rsad2 and Colec11 in our high fat diet fed BXD RI strains carrying the alternative B6 and D2 alleles of the respective genes revealed 1.4 times higher mRNA amounts of Rsad2 of D2 carriers (p=0.03), while no expression difference was found for Colec11 (p=0.10) (Figure 4). These results suggest cis-acting genetic variation that interacts with environmental changes on the cellular level leading to differential gene activation of Rsad2 under different diets.

Bottom Line: Obesity-associated organ-specific pathological states can be ensued from the dysregulation of the functions of the adipose tissues, liver and muscle.The analysis of genotype-phenotype correlations revealed significant quantitative trait loci (QTL) on chromosome 12 for the content of fat and collagen, collagen integrity, and the lipid to protein ratio in adipose tissue and on chromosome 17 for lipid to protein ratio in liver.The candidate genes in the QTL regions may contribute to obesity-related diseases in humans, in particular if the results can be verified in a bigger BXD cohort.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department for Crop and Animal Sciences, Humboldt-Universität zu Berlin, Invalidenstraße 42, 10115, Berlin, Germany.

ABSTRACT

Background: Obesity-associated organ-specific pathological states can be ensued from the dysregulation of the functions of the adipose tissues, liver and muscle. However, the influence of genetic differences underlying gross-compositional differences in these tissues is largely unknown. In the present study, the analytical method of ATR-FTIR spectroscopy has been combined with a genetic approach to identify genetic differences responsible for phenotypic alterations in adipose, liver and muscle tissues.

Results: Mice from 29 BXD recombinant inbred mouse strains were put on high fat diet and gross-compositional changes in adipose, liver and muscle tissues were measured by ATR-FTIR spectroscopy. The analysis of genotype-phenotype correlations revealed significant quantitative trait loci (QTL) on chromosome 12 for the content of fat and collagen, collagen integrity, and the lipid to protein ratio in adipose tissue and on chromosome 17 for lipid to protein ratio in liver. Using gene expression and sequence information, we suggest Rsad2 (viperin) and Colec11 (collectin-11) on chromosome 12 as potential quantitative trait candidate genes. Rsad2 may act as a modulator of lipid droplet contents and lipid biosynthesis; Colec11 might play a role in apoptopic cell clearance and maintenance of adipose tissue. An increased level of Rsad2 transcripts in adipose tissue of DBA/2J compared to C57BL/6J mice suggests a cis-acting genetic variant leading to differential gene activation.

Conclusion: The results demonstrate that the analytical method of ATR-FTIR spectroscopy effectively contributed to decompose the macromolecular composition of tissues that accumulate fat and to link this information with genetic determinants. The candidate genes in the QTL regions may contribute to obesity-related diseases in humans, in particular if the results can be verified in a bigger BXD cohort.

Show MeSH
Related in: MedlinePlus