Analysis of novel obesity genes with the aid of congenic rats

Background: Obesity is caused by multiple genes and their interaction. Studies in rats have revealed a link between a number of quantitative trait loci (QTLs) with facets of the metabolic syndrome. A QTL for serum cholesterol and body weight was identified on rat chromosome 10.

Methods: We generated a congenic rat strain, DA.WOKW10 and new sub-congenic rat strains (L1, L2, L3) for rat chromosome 10. Phenotyping and genotyping comparison of L1, L2 and L3 rat lines compared to parental strains have been performed. Phenotyping includes body weight gain up to an age of 30 weeks. Per strain and gender 10 rats have been studied. At the end of observation period we analyzed serum levels of leptin, adiponectin, insulin and c-pepdide, and serum lipid profile as well as relative adipose tissue weight. We examined body fat composition by using Echo-MRI, fat cell size distribution and morphological changes with histological stainings. Gene expression analysis was realized with 2D gel electrophoresis and RNA expression analysis using RT-PCR.

Results: Males of sub-congenic rats (L1, L2, L3) showed an increased in body weight compared to parental strain, DA rats. In contrast, female sub-congenic rats (L1, L2, L3) were lighter than the parental strain. We could also observe alterations in insulin and c-peptide levels as well as in the lipid profile. These results indicate that the involved genes on rat chromosome 10 have sex specific roles. After gene expression analysis in adipose tissue and liver of DA.WOKW10 rats and sub-congenics we selected potential candidate genes for further functional testing.

Conclusion: With the aid of sub-congenic rat lines we could shorten down the region on rat chromosome 10 and could select potential candidate genes for further functional studies in adipose tissue.