Hepatocyte activity of the cholesterol sensor smoothened regulates cholesterol and bile acid homeostasis in mice
| Autor: | Valentin Gogonea, George D. Dalton, Amanda L. Brown, Anna Mae Diehl, Seh-Hoon Oh, Stephanie Zhang, Preeti Pathak, Camelia Baleanu-Gogonea, Linda Tang, Venkateshwari Varadharajan, J. Mark Brown |
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| Rok vydání: | 2021 |
| Předmět: |
Multidisciplinary
Bile acid Molecular biology Chemistry Cholesterol medicine.drug_class Science Endoplasmic reticulum Lipid Sterol Sterol regulatory element-binding protein Cell biology chemistry.chemical_compound medicine.anatomical_structure Hepatocyte medicine lipids (amino acids peptides and proteins) Smoothened Liver X receptor Molecular physiology |
| Zdroj: | iScience, Vol 24, Iss 9, Pp 103089-(2021) |
| ISSN: | 2589-0042 |
| Popis: | Summary: 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. |
| Databáze: | OpenAIRE |
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