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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE101116 | GEO | 2017/12/03

SECONDARY ACCESSION(S): PRJNA393729

REPOSITORIES: GEO

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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 [seq]

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

2017-12-03 | GSE101115 | GEO

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

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

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

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The tight junction protein TJP1 regulates the feeding-modulated hepatic circadian clock.

Project description:Circadian clocks in the suprachiasmatic nucleus and peripheral tissues orchestrate behavioral and physiological activities of mammals in response to environmental cues. In the liver, the circadian clock is also modulated by feeding. However, the molecular mechanisms involved are unclear. Here, we show that TJP1 (tight junction protein 1) functions as a mediator of mTOR (mechanistic target of rapamycin) to modulate the hepatic circadian clock. TJP1 interacts with PER1 (period circadian regulator 1) and prevents its nuclear translocation. During feeding, mTOR phosphorylates TJP1 and attenuates its association with PER1, thereby enhancing nuclear shuttling of PER1 to dampen circadian oscillation. Therefore, our results provide a previously uncharacterized mechanistic insight into how feeding modulates the hepatic circadian clock.

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BBX19 fine-tunes the circadian rhythm by interacting with PSEUDO-RESPONSE REGULATOR proteins to facilitate their repressive effect on morning-phased clock genes.

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Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression.

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Feeding schedule and the circadian clock shape rhythms in hepatic gene expression

Project description:This SuperSeries is composed of the following subset Series: GSE13060: The effects of temporally restricted feeding on hepatic gene expression GSE13062: The effects of temporally restricted feeding on hepatic gene expression of Cry1, Cry2 double KO mice GSE13063: Effects of extensive fasting and subsequent feeding on hepatic transcription GSE13064: Effects of extensive fasting on hepatic transcription Refer to individual Series

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Feeding schedule and the circadian clock shape rhythms in hepatic gene expression

Project description:This SuperSeries is composed of the SubSeries listed below.

2009-11-12 | GSE13093 | GEO