Abstract
BackgroundObesity-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.ResultsMice 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.ConclusionThe 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.
Highlights
Obesity-associated organ-specific pathological states can be ensued from the dysregulation of the functions of the adipose tissues, liver and muscle
Phenotypes of parental and BXD recombinant inbred (RI) strains on high fat diet After feeding a high fat diet over 16 weeks, between C57BL/6J (B6) males gained more weight compared to D2 males (Figure 1a)
They had more than two-fold higher relative contents of total fat, saturated fat, unsaturated fat, collagen and lipid to protein ratio (Table 1) and 0.5 fold lower relative collagen integrity in the adipose tissue
Summary
Obesity-associated organ-specific pathological states can be ensued from the dysregulation of the functions of the adipose tissues, liver and muscle. Chromatographic techniques (gas chromatography, HPLC) [13], different biochemical reagent sets [8], or enzymatic assays [10] are used for metabolic profiling to obtain information about specific components such as cholesterol, triglycerides, glycerol and others. Most of these methods are time consuming and not suitable for liquid and solid samples without preparation. They cannot specify structural and compositional changes in the samples, simultaneously
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