Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.20.256487v1?rss=1 Authors: Moldavski, O., Zushin, P.-J. H., Berdan, C. A., van Eijkeren, R. J., Jiang, X., Qian, M., Ory, D. S., Covey, D. F., Nomura, D., Stahl, A., Weiss, E., Zoncu, R. Abstract: Oxysterols are oxidized derivatives of cholesterol that play signaling roles in lipid biosynthesis and homeostasis. Here we show that 4{beta}-hydroxycholesterol (4{beta}-HC), a liver and serum abundant oxysterol of poorly defined function, is a potent and selective inducer of the master lipogenic transcription factor, Sterol Regulatory Element Binding Protein 1c (SREBP1c), but not the related steroidogenic transcription factor SREBP2. Mechanistically, 4{beta}-HC acts as a putative agonist for Liver X receptor (LXR), a sterol sensor and transcriptional regulator previously linked to SREBP1c activation. Unique among the oxysterol agonists of LXR, 4{beta}-HC induced expression of the lipogenic program downstream of SREBP1c, and triggered de novo lipogenesis both in primary hepatocytes and in mouse liver. 4{beta}-HC- acted in parallel to insulin-PI3K-dependent signaling to stimulate triglyceride synthesis and lipid droplet accumulation. Thus, 4{beta}-HC is an endogenous regulator of de novo lipogenesis through the LXR-SREBP1c axis. Copy rights belong to original authors. Visit the link for more info