| First Author | Guan D | Year | 2023 |
| Journal | J Clin Invest | Volume | 133 |
| Issue | 8 | PubMed ID | 37066875 |
| Mgi Jnum | J:335125 | Mgi Id | MGI:7466056 |
| Doi | 10.1172/JCI163018 | Citation | Guan D, et al. (2023) Hepatocyte SREBP signaling mediates clock communication within the liver. J Clin Invest 133(8) |
| abstractText | 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-erbalpha and -beta (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-ERBalpha and beta (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. |
