Journal article
Hepatocyte SREBP signaling mediates clock communication within the liver
The Journal of clinical investigation, Vol.133(8), pp.1-10
04/15/2023
DOI: 10.1172/JCI163018
PMID: 37066875
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.
Details
- Title: Subtitle
- Hepatocyte SREBP signaling mediates clock communication within the liver
- Creators
- Dongyin Guan - Baylor College of MedicineHosung Bae - University of California, IrvineDishu Zhou - Baylor College of MedicineYing Chen - Baylor College of MedicineChunjie Jiang - Baylor College of MedicineCam Mong La - Baylor College of MedicineYang Xiao - University of PennsylvaniaKun Zhu - University of PennsylvaniaWenxiang Hu - University of PennsylvaniaTrang Minh Trinh - University of PennsylvaniaPanpan Liu - Baylor College of MedicineYing Xiong - University of PennsylvaniaBishuang Cai - Icahn School of Medicine at Mount SinaiCholsoon Jang - University of California, IrvineMitchell A. Lazar - University of Pennsylvania
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.133(8), pp.1-10
- DOI
- 10.1172/JCI163018
- PMID
- 37066875
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Publisher
- American Society for Clinical Investigation
- Grant note
- R01DK45586,K01-DK125602,P30 DK19525,DK056338,R00DK115778 / NIDDK R01-DK045586,K01-DK125602,R01-AA029124,P30 DK19525 / ;
- Language
- English
- Date published
- 04/15/2023
- Academic Unit
- Internal Medicine
- Record Identifier
- 9985217034902771
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