Cargando…

The hepatic circadian clock fine-tunes the lipogenic response to feeding through RORα/γ

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 RORα and RORγ, key components of the molecular circadian clock, up-regulate exp...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Yuxiang, Papazyan, Romeo, Damle, Manashree, Fang, Bin, Jager, Jennifer, Feng, Dan, Peed, Lindsey C., Guan, Dongyin, Sun, Zheng, Lazar, Mitchell A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5558923/
https://www.ncbi.nlm.nih.gov/pubmed/28747429
http://dx.doi.org/10.1101/gad.302323.117
Descripción
Sumario: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 RORα and RORγ, 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. RORα/γ controls circadian expression of Insig2, which keeps feeding-induced SREBP1c activation under check. Loss of RORα/γ 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.