Expression of SREBP-1c Requires SREBP-2-mediated Generation of a Sterol Ligand for LXR in Livers of Mice

• DOI: 10.7554/elife.25015
• Publication Date: 2017-02-28T13:02:09Z
• Authors: Shunxing Rong; Víctor A Cortés; Shirya Rashid; Norma N Anderson; Jeffrey G McDonald; Guosheng Liang; Young-Ah Moon; Robert E Hammer; Jay D Horton
• Keywords: Liver X receptor

The synthesis of cholesterol and fatty acids (FA) in the liver is independently regulated by SREBP-2 SREBP-1c, respectively. Here, we genetically deleted Srebf-2 from hepatocytes confirmed that regulates all genes involved biosynthesis, LDL receptor, PCSK9; a secreted protein degrades receptors liver. Surprisingly, found elimination mice also markedly reduced SREBP-1c expression FA triglyceride are normally SREBP-1c. nuclear receptor LXR necessary for Srebf-1c transcription. deletion subsequent lower sterol eliminated production an endogenous ligand required activity expression. These studies demonstrate coupled flux through biosynthetic pathway maximal high rates synthesis.