Abstract
BackgroundGenome-wide association studies (GWAS) are useful to reveal an association between single nucleotide polymorphisms and different measures of obesity. A multitude of new loci has recently been reported, but the exact function of most of the according genes is not known. The aim of our study was to start elucidating the function of some of these genes.MethodsWe performed an expression analysis of fourteen genes, namely BDNF, ETV5, FAIM2, FTO, GNPDA2, KCTD15, LYPLAL1, MCR4, MTCH2, NEGR1, NRXN3, TMEM18, SEC16B and TFAP2B, via real-time RT-PCR in adipose tissue of the kidney capsule, the mesenterium and subcutaneum as well as the hypothalamus of obese Zucker diabetic fatty (ZDF) and Zucker lean (ZL) rats at an age of 22 weeks.ResultsAll of our target genes except for SEC16B showed the highest expression in the hypothalamus. This suggests a critical role of these obesity-related genes in the central regulation of energy balance. Interestingly, the expression pattern in the hypothalamus showed no differences between obese ZDF and lean ZL rats. However, LYPLAL1, TFAP2B, SEC16B and FAIM2 were significantly lower expressed in the kidney fat of ZDF than ZL rats. NEGR1 was even lower expressed in subcutaneous and mesenterial fat, while MTCH2 was higher expressed in the subcutaneous and mesenterial fat of ZDF rats.ConclusionThe expression pattern of the investigated obesity genes implies for most of them a role in the central regulation of energy balance, but for some also a role in the adipose tissue itself. For the development of the ZDF phenotype peripheral rather than central mechanisms of the investigated genes seem to be relevant.
Highlights
Genome-wide association studies (GWAS) are useful to reveal an association between single nucleotide polymorphisms and different measures of obesity
Genome-wide association studies (GWAS) are excellently qualified to reveal single genetic polymorphisms associated with human obesity, but they allow no conclusions about the function of the affected genes
The aim of our study was to shed some light in the role of fourteen recently described genes, namely BDNF, ETV5, FAIM2, FTO, GNPDA2, KCTD15, LYPLAL1, MCR4, MTCH2, NEGR1, NRXN3, TMEM18, SEC16B, and TFAP2B, which were associated with different measures of human obesity
Summary
Genome-wide association studies (GWAS) are useful to reveal an association between single nucleotide polymorphisms and different measures of obesity. Overweight and obesity have become a major public health problem in the industrialized world and in developing countries. Both result in an increased morbidity and mortality, not to mention the financial costs for the health-care systems. Thereby, Genome-wide association studies (GWAS) are excellently qualified to reveal single genetic polymorphisms associated with human obesity, but they allow no conclusions about the function of the affected genes. Our study was planned as a descriptive expression analysis of these obesity-related genes in an animal model of diabetes mellitus type 2 and obesity, the ZDF rat, in comparison to their lean normoglycemic littermate, the ZL rat
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