Nevertheless, these results were unexpected as recent studies in humans, based either on microarray data and on the analysis of the expression of specific proteins involved in lipolysis or lipogenesis, suggest that both processes are decreased in severely obese subjects. In this scenario, it is tempting to speculate that the enhanced expression of Rab18 in obese individuals is an adaptive response to overcome the alterations in lipid metabolism occurring in obesity. Finally, although we observed a tendency toward lower Rab18 mRNA expression in obese T2D individuals compared to obese NG and IGT patients, there does not appear to be an apparent association between the expression of this GTPase and insulin sensitivity. In conclusion, our data provide novel insights concerning the distribution and function of Rab18 in adipocytes. Specifically, through its interaction with the surface of LDs and, most likely, with ER membranes, Rab18 regulates adipocyte lipid metabolism in response to bothGW786034 msds lipogenic and lipolytic inputs. In humans, Rab18 is associated with the surface of LDs in adipocytes and its expression in adipose tissue, which displays sexand depot-related differences, correlates with increased adiposity, providing evidence for the participation of this GTPase in the regulation of human adipocyte biology under both normal and pathological conditions. Friedreich ataxia is an autosomal recessive disorder characterized by neurodegeneration and cardiomyopathy. It is the most common form of hereditary ataxia with an estimated 2–3 affected individuals per 100,000 in European populations and an estimated carrier frequency of 1 in 110. The causative gene, FXN, is located on the long arm of chromosome 9. The FXN gene encodes the mitochondrial protein frataxin, which plays an important role in iron-sulfur cluster biogenesis. Homozygosity for a GAA trinucleotide repeat expansion within the first intron of the FXN gene is the most common Ibrutinibcause of FRDA. Normal alleles contain 6–34 uninterrupted GAA repeats. The majority of individuals with FRDA have between 67 to over 1,300 GAA repeats in both FXN alleles. The nontranslated GAA repeat expansion results in inhibition of gene expression and an insufficiency of frataxin. An inverse correlation exists between the size of the smaller expanded allele and transcript levels, the amount of residual frataxin produced and the age of onset of disease symptoms. Heterozygous carriers of a GAA repeat expansion produce about half the normal level of frataxin and are asymptomatic. As the GAA repeat expansion mutation does not alter the coding sequence of the gene, it is hypothesized that any increase in frataxin levels should prove beneficial, while a several-fold increase could be sufficient to halt disease progression. There is currently limited information on the regulation of the FXN gene. The 1,255 bp region upstream of the FXN coding region contains the minimal promoter.