| First Author | Zhang Y | Year | 2017 |
| Journal | Genes Dev | PubMed ID | 28747429 |
| Mgi Jnum | J:244377 | Mgi Id | MGI:5913156 |
| Doi | 10.1101/gad.302323.117 | Citation | Zhang Y, et al. (2017) The hepatic circadian clock fine-tunes the lipogenic response to feeding through RORalpha/gamma. Genes Dev |
| abstractText | Liver lipid metabolism is under intricate temporal control by both the circadian clock and feeding. The interplay between these two mechanisms is not clear. Here we show that liver-specific depletion of nuclear receptors RORalpha and RORgamma, key components of the molecular circadian clock, up-regulate expression of lipogenic genes only under fed conditions at Zeitgeber time 22 (ZT22) but not under fasting conditions at ZT22 or ad libitum conditions at ZT10. RORalpha/gamma controls circadian expression of Insig2, which keeps feeding-induced SREBP1c activation under check. Loss of RORalpha/gamma causes overactivation of the SREBP-dependent lipogenic response to feeding, exacerbating diet-induced hepatic steatosis. These findings thus establish ROR/INSIG2/SREBP as a molecular pathway by which circadian clock components anticipatorily regulate lipogenic responses to feeding. This highlights the importance of time of day as a consideration in the treatment of liver metabolic disorders. |
