Hepatocyte SREBP signaling mediates clock communication within the liver
Dongyin Guan, … , Cholsoon Jang, Mitchell A. Lazar
Dongyin Guan, … , Cholsoon Jang, Mitchell A. Lazar
Published April 17, 2023
Citation Information: J Clin Invest. 2023;133(8):e163018. https://doi.org/10.1172/JCI163018.
View: Text | PDF
Research Article Hepatology Metabolism

Hepatocyte SREBP signaling mediates clock communication within the liver

Abstract

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.

Authors

Dongyin Guan, Hosung Bae, Dishu Zhou, Ying Chen, Chunjie Jiang, Cam Mong La, Yang Xiao, Kun Zhu, Wenxiang Hu, Trang Minh Trinh, Panpan Liu, Ying Xiong, Bishuang Cai, Cholsoon Jang, Mitchell A. Lazar

×
Problems with a PDF?

This file is in Adobe Acrobat (PDF) format. If you have not installed and configured the Adobe Acrobat Reader on your system.

Having trouble reading a PDF?

PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.

Having trouble saving a PDF?

Many versions of the free Acrobat Reader do not allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users: Right-click on the Download link and choose the option that says something like "Save Link As...". Mac users should hold the mouse button down on the link to get these same options.

Having trouble printing a PDF?

  1. Try printing one page at a time or to a newer printer.
  2. Try saving the file to disk before printing rather than opening it "on the fly." This requires that you configure your browser to "Save" rather than "Launch Application" for the file type "application/pdf", and can usually be done in the "Helper Applications" options.
  3. Make sure you are using the latest version of Adobe's Acrobat Reader.

Supplemental data - Download (7.64 MB)

Advertisement