Expression of SREBP-lc Requires SREBP2-mediated Generation of a Sterol Ligand for LXR in Livers of Mice

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dc.contributor.authorRong, Shunxing
dc.contributor.authorCortes, Victor A.
dc.contributor.authorRashid, Shirya
dc.contributor.authorAnderson, Norma N.
dc.contributor.authorMcDonald, Jeffrey G.
dc.contributor.authorLiang, Guosheng
dc.contributor.authorMoon, Young-Ah
dc.contributor.authorHammer, Robert E.
dc.contributor.authorHorton, Jay D.
dc.date.accessioned2025-01-23T21:26:45Z
dc.date.available2025-01-23T21:26:45Z
dc.date.issued2017
dc.description.abstractThe synthesis of cholesterol and fatty acids (FA) in the liver is independently regulated by SREBP-2 and SREBP-1c, respectively. Here, we genetically deleted Srebf-2 from hepatocytes and confirmed that SREBP-2 regulates all genes involved in cholesterol biosynthesis, the LDL receptor, and PCSK9; a secreted protein that degrades LDL receptors in the liver. Surprisingly, we found that elimination of Srebf-2 in hepatocytes of mice also markedly reduced SREBP-1c and the expression of all genes involved in FA and triglyceride synthesis that are normally regulated by SREBP-1c. The nuclear receptor LXR is necessary for Srebf-1c transcription. The deletion of Srebf-2 and subsequent lower sterol synthesis in hepatocytes eliminated the production of an endogenous sterol ligand required for LXR activity and SREBP-lc expression. These studies demonstrate that cholesterol and FA synthesis in hepatocytes are coupled and that flux through the cholesterol biosynthetic pathway is required for the maximal SREBP-1c expression and high rates of FA synthesis.
dc.fuente.origenWOS
dc.identifier.doi10.7554/eLife.25015.001
dc.identifier.issn2050-084X
dc.identifier.urihttps://doi.org/10.7554/eLife.25015.001
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/101363
dc.identifier.wosidWOS:000397617400001
dc.language.isoen
dc.revistaElife
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleExpression of SREBP-lc Requires SREBP2-mediated Generation of a Sterol Ligand for LXR in Livers of Mice
dc.typeartículo
dc.volumen6
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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