Genes regulated in the three states fed, fasted and sibu tramine treated were similarly affected by the diurnal signal. In the assessment of diurnal regulation by correlation to PER1, a high degree of correlation among the three states was observed, indicating that the largest effect on the transcriptome is the time of day and not Calcitriol proliferation any other perturbations. nevertheless, there were 500 genes with significantly different correlations to PER1 among the three states. Impact of food restriction on the transcriptional profile of the adipose tissue Further investigation of genes that were differentially reg ulated between fasting and feeding at the 6 hour pre meal time point demonstrated that 498 genes were differen tially expressed between the fasted and fed arms .

318 genes had higher correlations and 180 had lower correlations in the fasted arm compared with the fed arm. Despite the small difference between the fasted and fed arms, the association with the diurnal signature as measured by PER1 correlation was significant. Overall, 94% of the genes with expression lev els affected by food intake were correlated to PER1 expres sion. In addition, genes that were upregulated in the fasting arm were positively correlated with PER1 expression and genes that were upregulated in the fed arm were negatively correlated with PER1. Because these signa ture genes were also correlated with PER1, the fasting arm positively affected the genes that were on the diurnal decline, whereas the fed arm positively affected the genes that were on the diurnal incline.

Genes that were differentially regulated between the fasted and fed treatment arms at the 6 hour timepoint continued to be regulated at the 10 hour time point in the fasted arm, but not in the fed arm. Several genes that were regulated by fasting in this study formed a highly connected node in the Ingenuity net work, indicating that these genes have been found to be biologically inter connected in other independent studies. In this tight network, the gene oncostatin, a mac rophage expressed gene, was downregulated 2 fold in the fasted state compared with the fed state. Forming Drug_discovery a network with OSM are other genes that U0126 MAPK are also downreg ulated by fasting, such as LDLR, MMP3, EGR1 and IL8. Although the inflammatory genes overall were on the incline with the diurnal rhythm, the inflammatory genes were more downregulated in the fasted state, suggesting that fasting delays the diurnal rhythm by dampening the upward climb of the expression of these inflammatory genes. Icelandic replication analysis With the aim of validating the fasting and feeding signa tures of the present study, we analyzed another com pletely independent study carried out on 20 Icelandic subjects.