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The hepatic circadian clock fine-tunes the lipogenic response to feeding through RORa/g [array]

ABSTRACT: We address the function of ROR in the mouse liver metabolism

ORGANISM(S): Mus musculus

PROVIDER: GSE101079 | GEO | 2017/12/03

SECONDARY ACCESSION(S): PRJNA393689

REPOSITORIES: GEO

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The hepatic circadian clock fine-tunes the lipogenic response to feeding through RORa/g [seq]

Project description:We address the function of ROR in the mouse liver metabolism

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The hepatic circadian clock fine-tunes the lipogenic response to feeding through RORa/g

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

Project description: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.

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The hepatic circadian clock fine-tunes the lipogenic response to feeding through RORa/g

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