Demonstrates that oxytocin neurons are required for diet induced energy expenditure but are not necessary for food intake regulation. Moreover, whereas oxytocin neurons are required for a full physiologic response to leptin administration, they are dispensable for the anoretic action of melanocortin agonists. This suggests that additional, non-oxytocin dependent neural circuits play important roles in the regulation of food intake. It is important to note that although related, depression, fatigue and QoL are distinct concepts. In our study both mental QoL and vitality were independently, negatively related to CXCL9 and CXCL11 expression levels. These cytokines belong to the same family together with CXCL10 and share the common receptor CXCR3. In normal conditions their CHIR-99021 levels are generally not detectable but are strongly induced by interferongamma. Previous research has demonstrated that global QoL was negatively related to IFN-c. Serum levels of the related CXCL10 gene were found to be related to depression. Additionally, in our patient population vitality was negatively related to the IFNA6 gene. Although there is little known about the function of this gene, IFN-induced fatigue is a common phenomenon. Interestingly, the SNPs in CXCL9, CXCL10, CXCL11 and IFN genes were not significantly associated with QoL. High expression levels of these genes are most likely induced by other inflammatory genes up-stream in a complex immunological cascade. In line with this hypothesis, we found a relation between mental QoL and SNPs in the IL4R gene. This gene codes for the IL4 receptor. Polymorphisms in this gene are associated with asthma and rhinitis in case-control studies. In our patient population the prevalence of immunological and allergic disorders was not increased suggesting SNPs in the IL4R gene independently contributed to mental QoL. Numerous studies have shown that higher IL4 levels are protective for depression. Mechanisms through which inflammatory genes and QoL are related are unknown. Hypothetically, high expression levels of cytokine-related genes are associated with sickness-behavior which is reflected in impaired QoL. In our previous work we found that inflammation aggravates disease severity in MFS patients. In this study however, mental QoL was associated with cytokine related genes independently of disease characteristics, suggesting an independent immune-related process which affects the perception of the well-being in these patients. Functional immunological studies are needed in order to elucidate the exact mechanism of this relation. Although mental QoL and vitality were unrelated to MFS, there was a high number of patients, approximately 10%, with low scores for these two components of mental QoL. These patients showed high systemic levels of the CCL11. Similar results have been found in depressed patients; they showed elevated CCL11 levels compared to age- and gender-matched controls. In this study only clinically treated depression was documented. We cannot exclude the possibility that some patients with low QoL have depressive symptoms. Other factors which were not measured in this study could also contribute to QoL impairments. For example, MFS patients are likely to have emotional problems, such as feelings of guilt because of inheritance of MFS and concerns about their career, family planning, insurance and housing. In addition, factors not related to MFS, such as lack of social support and personality may play a role as well. Future studies should explore additional factors associated with QoL in MFS patients.