Hepatocyte SREBP signaling mediates clock communication within the liver. J Clin Invest 2023 Apr 17;133(8)
Date
04/18/2023Pubmed ID
37066875Pubmed Central ID
PMC10104893DOI
10.1172/JCI163018Scopus ID
2-s2.0-85152629595 (requires institutional sign-in at Scopus site) 29 CitationsAbstract
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.
Author List
Guan D, Bae H, Zhou D, Chen Y, Jiang C, La CM, Xiao Y, Zhu K, Hu W, Trinh TM, Liu P, Xiong Y, Cai B, Jang C, Lazar MAAuthor
Yang Xiao Assistant Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Circadian RhythmCommunication
Hepatocytes
Liver
Nuclear Receptor Subfamily 1, Group D, Member 1
Sterol Regulatory Element Binding Protein 1
