Food entrainment of circadian gene expression altered in PPARalpha-/- brown fat and heart.

The circadian clock is subject to food entrainment. Since PPARalpha exhibits a circadian expression profile, we hypothesized that PPARalpha deficiency would alter the food entrainable response of adipose, cardiac, and liver tissues. Wild-type and PPARalpha null mice were compared under ad libitum or restricted food access for the expression of circadian transcription factor-encoding mRNAs. Temporally restricted food access caused between a mean 5.8-11.5 h phase shift in the expression profiles of the circadian genes Bmal1, Per3, and Rev-erbalpha in all tissues of control mice. In contrast, these same conditions phase shifted the circadian genes in tissues of PPARalpha null mice between a mean of 10.8-14.2 h with amplitude attenuation. The food entrained phase shifts in the brown adipose and cardiac tissue circadian transcription factors of the PPARalpha null mice were prolonged significantly relative to wild-type controls. Likewise, PPARalpha responsive genes in the livers of PPARalpha null mice exhibited a significantly prolonged phase shift relative to control mice. These findings confirm and extend recent observations in the literature.