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Hepatocyte SREBP signaling mediates clock communication within the liver

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

ORGANISM(S): Mus musculus

PROVIDER: GSE206319 | GEO | 2023/04/03

REPOSITORIES: GEO

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Hepatocyte SREBP signaling mediates clock communication within the liver.

Project description:Rhythmic intraorgan communication coordinates environmental signals and the cell-intrinsic clock to maintain organ homeostasis. Hepatocyte-specific KO of core components of the molecular clock Rev-erbα and -β (Reverb-hDKO) alters cholesterol and lipid metabolism in hepatocytes as well as rhythmic gene expression in nonparenchymal cells (NPCs) of the liver. Here, we report that in fatty liver caused by diet-induced obesity (DIO), hepatocyte SREBP cleavage-activating protein (SCAP) was required for Reverb-hDKO-induced diurnal rhythmic remodeling and epigenomic reprogramming in liver macrophages (LMs). Integrative analyses of isolated hepatocytes and LMs revealed that SCAP-dependent lipidomic changes in REV-ERB-depleted hepatocytes led to the enhancement of LM metabolic rhythms. Hepatocytic loss of REV-ERBα and β (REV-ERBs) also attenuated LM rhythms via SCAP-independent polypeptide secretion. These results shed light on the signaling mechanisms by which hepatocytes regulate diurnal rhythms in NPCs in fatty liver disease caused by DIO.

| S-EPMC10104893 | biostudies-literature

Hepatocyte SREBP signaling mediates clock communication within the liver [ATAC-seq]

Project description:Rhythmic intraorgan communication coordinates environmental signals and cell-intrinsic clock to maintain organ homeostasis. Hepatocyte-specific knockout of core components of the molecular clock, Rev-erba and b (ReverbhDKO), alters cholesterol and lipid metabolism in hepatocytes as well as rhythmic gene expression in non-parenchymal cells (NPC) of the liver. Here we report that in diet induced obesity (DIO)-caused fatty liver, hepatocyte SREBP cleavage-activating protein (SCAP) is required for ReverbhDKO-induced diurnal rhythmic remodeling and epigenomic reprogramming in Kupffer cells (KC). Integrative analyses of isolated hepatocytes and Kupffer cells uncovered potential signals, including secreted polypeptides and metabolites, that gain rhythmicity in the absence of REV-ERBs in a SCAP-dependent manner. These results shed light on the signaling mechanisms by which hepatocytes regulate diurnal rhythms in NPCs in DIO and fatty liver disease.

2023-04-04 | GSE206318 | GEO

Hepatocyte SREBP signaling mediates clock communication within the liver [scRNA-seq]

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Hepatocyte SREBP signaling mediates clock communication within the liver [RNA-seq]

2023-04-04 | GSE206316 | GEO

Hepatocyte SREBP signaling mediates clock communication within the liver

Project description:Hepatocyte SREBP signaling mediates clock communication within the liver

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Hepatocyte SREBP signaling mediates clock communication within the liver [RNA-seq]

Project description:Hepatocyte SREBP signaling mediates clock communication within the liver [RNA-seq]

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Hepatocyte SREBP signaling mediates clock communication within the liver [scRNA-seq]