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vol. 51
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issue 2
193-197
EN
The melanocortin-4 receptor (Mc4r) plays an important role in body-weight regulation. This study examines the methylation status and expression levels of the Mc4r gene in response to a standard and a high-fat diet in the obese Berlin fat mouse inbred (BFMI) line and the lean C57BL/6NCrl (B6) line of Mus musculus. The methylation status of CpG sites located within the Mc4r exon was analyzed by bisulfite genomic sequencing of genomic DNA of brain tissues, and gene expression analysis was performed by real-time PCR. In both lines, the methylation of CpGs 1-8 (near the transcription start) was lower than methylation of CpGs 9-16 (located towards the end of the selected amplicon). On the standard diet, the methylation status did not differ between the lines. In response to high-fat diet, methylation of the CpGs near the transcription start was decreased in both lines. The Mc4r gene expression, however, was only marginally increased in BMFI mice, whereas there was no change in B6 mice. The results suggest that a long-term high-fat diet might have an effect on the methylation status of the Mc4r gene. However, the effect of methylation on Mc4r expression seems to be a variable compensated by other regulating factors in a line-specific manner.
EN
Recently, quantitative trait loci (QTLs) for body weight and obesity have been mapped in an intercross population between the high body weight-selected mouse line DU6i and the inbred line DBA/2. Most QTLs were highly significant, but had small effects only. Under the hypothesis that small-effect QTLs might result from changes in gene activity, our strategy to identify candidate genes for the observed effects was directed towards the identification of differentially expressed genes. Therefore, here we compare the transcription profile of about 11 000 genes in epididymal fat tissues of males of two high body weight-selected (DU6 and DU6i) and two unselected mouse lines (DUKs and DBA/2). For the hybridisation of GeneChips, we used pooled samples of 20 individual mice. By pair-wise comparisons between selected and unselected mouse lines, a set of 77 genes was identified representing genes whose level of expression differed between obese and lean mouse strains. According to the functional classification of genes, 69 differentially expressed genes were involved in regulatory and metabolic pathways, cell division, cell stability, or immune response, and thus might have an effect on body weight and fat accumulation. 14 out of these genes, occur in QTL regions for body weight or abdominal fat weight. Further analyses are necessary to discriminate between genes directly causing QTL effects and indirectly regulated differentially expressed genes.
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