For the other E-box driven genes studied herein, namely those involved in interactions between the clock and metabolism, i.e., Dbp, E4bp4 and Nampt, the advance was subtle and the amplitude was only slightly decreased. Similarly to that of Wee1, the expression profile of none of these genes did differ between the two rat strains under ad libitum feeding. Under RF conditions, the expression of Prkab2 exhibited a circadian oscillation in the SHR but was not rhythmic in the Wistar rats. The results also demonstrated that under RF, expression profiles of some studied genes in the liver of SHR were suppressed or did not differ compared with those in Wistar rats. This might be because these genes are not driven by the clock but rather by changes in the metabolic state. The RF likely affected the metabolic state of the SHR Perifosine moa differently than the Wistar rats because the constitutive expression of Pgc1��, which coordinates the transcriptional programs important for energy metabolism and homeostasis, was significantly suppressed in the SHR compared with the Wistar rats. Pgc1�� encodes a Temozolomide Autophagy inhibitor co-activator that enhances the activity of many nuclear receptors, including PPAR��. It is noteworthy that the Ppara expression was also slightly suppressed in the SHRs but became expressed rhythmically in response to RF, though with a low amplitude. The observed suppression was not due to a lower strain-specific basal expression of these genes under ad libitum conditions. The significant suppression of Pgc1�� and Ppara expression may likely result in decreased levels of the PPAR��/PGC1�� transcriptional complex with nuclear receptors, which may consequently affect the activity of downstream genes regulating fatty acid uptake and oxidation in the liver of SHR maintained under RF. The other metabolism-relevant gene expression profiles in the liver did not differ between the two strains, namely that of Pparg, Hdac3, Hif1a and Ppp1r3c. Thus, the data suggest that RF impacts the metabolic state in the liver of SHR differently than in Wistar rats, with the most obvious difference in the suppression of Pgc1�� and Ppara expression and the imposition of a low-amplitude rhythmicity in Ppara and Prkab2 expression. These changes in gene expression might have a broad impact on the transcription of variety of genes, including those whose products feed back on the circadian clock mechanism. We hypothesize that as a consequence, apart from other effects, the transcriptional activity of the Bmal2 gene may also have changed. Based on the limited data available, the likely pathways for this effect are highly speculative. To test the hypothesis that the abnormal metabolic state of SHR under RF may account for the higher sensitivity of their hepatic circadian clock to changes in the feeding regime, future studies should examine the suggested pathways at the level of protein expression and activities. It is also reasonable to consider the involvement of glucocorticoids, which are known to play a role in resetting the phase of the peripheral clock in the liver and whose peak levels are shifted due to RF in rats. The general hypersensitivity of the hypothalamic-pituitaryadrenal system of SHR might theoretically account for the facilitation of the hepatic clock response to RF. However, similar to the previously suggested pathways, the role of glucocorticoids in this effect has not been tested. In conclusion, our results demonstrate a previously unknown correlation between the extent of FAA and the phase-shifting of the peripheral clock in the liver. Additionally, our evidence that the putative food-entrainable oscillator driving the FAA is more sensitive in SHR may facilitate future studies aimed at localizing this clock in the mammalian body.