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Updated: Feb 25, 2026

Manipulation of Rhythmic Food Intake in Mice Using a Custom-Made Feeding System
Published on: December 16, 2022
The hepatic circadian clock fine-tunes the lipogenic response to feeding through RORα/γ
Yuxiang Zhang1,2,3, Romeo Papazyan1,2, Manashree Damle1,2
1Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Abstract:
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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