The liver is one of these organs, in particular in older mice. Increased fat accumulation in the liver can lead to development of hepatic insulin resistance. Therefore, the same mice as used for the pancreas analyses were Drostanolone Propionate chosen. Our analyses of body weight development of leptin-deficient mice within the first 10 weeks of their life have shown very clearly that FTO contributes to the gain of body weight. This result is very similar to the data of feeding leptin-wild type mice with different Fto genotypes with a high caloric diet. Thus, in both settings loss of FTO protects against obesity independent of the presence of leptin. However, our analysis also showed that leptindeficient mice older than 15 weeks gain more weight than wild type independent of the Fto genotype. This indicates that body weight development towards obesity is delayed by about three months when FTO is absent. Thus, leptin deficiency has a stronger effect than high fat diet and overrides the consequence of a 50% reduction of FTO. CCG-1423 Nevertheless, even in mice of 30 weeks of age we can monitor a significant difference between leptin-deficient mice with and without FTO. Certainly, it would be interesting to see whether even mice one year older still show a difference. In this respect also a conditional loss of FTO would be an attractive approach to see if a deletion of FTO in leptin-deficient mice at later time points can reverse or at least slow down the further development of the obese phenotype. Recently, several studies have addressed whether FTO in humans might be associated with the metabolic syndrome. However, the results are controversial. Whereas one study, concentrated on obese females, concluded no association, another using data from several studies, clearly showed an association of FTO with the metabolic syndrome. Nevertheless, several studies demonstrated a clear correlation between genetic variations of the FTO gene and an early development of obesity, which is the main cause for the metabolic syndrome. Having shown the relevance of FTO for the development of the metabolic syndrome in an animal model, which is supported by certain GWAS in humans, the question arises how FTO can be a target in the context of an anti-obesity therapy. To this end, a recent publication reported about a drug used in traditional Chinese medicine called rhein, which was most efficient among several substances tested.