| First Author | Dalton GD | Year | 2021 |
| Journal | iScience | Volume | 24 |
| Issue | 9 | Pages | 103089 |
| PubMed ID | 34568800 | Mgi Jnum | J:311868 |
| Mgi Id | MGI:6780787 | Doi | 10.1016/j.isci.2021.103089 |
| Citation | Dalton GD, et al. (2021) Hepatocyte activity of the cholesterol sensor smoothened regulates cholesterol and bile acid homeostasis in mice. iScience 24(9):103089 |
| abstractText | Cellular cholesterol is regulated by at least two transcriptional mechanisms involving sterol-regulatory-element-binding proteins (SREBPs) and liver X receptors (LXRs). Although SREBP and LXR pathways are the predominant mechanisms that sense cholesterol in the endoplasmic reticulum and nucleus to alter sterol-regulated gene expression, evidence suggests cholesterol in plasma membrane can be sensed by proteins in the Hedgehog (Hh) pathway which regulate organ self-renewal and are a morphogenic driver during embryonic development. Cholesterol interacts with the G-protein-coupled receptor Smoothened (Smo), which impacts downstream Hh signaling. Although evidence suggests cholesterol influences Hh signaling, it is not known whether Smo-dependent sterol sensing impacts cholesterol homeostasis in vivo. We examined dietary-cholesterol-induced reorganization of whole-body sterol and bile acid (BA) homeostasis in adult mice with inducible hepatocyte-specific Smo deletion. These studies demonstrate Smo in hepatocytes plays a regulatory role in sensing and feedback regulation of cholesterol balance driven by excess dietary cholesterol. |
