Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover

Goldstein, J. L. & Brown, M. S. A century of cholesterol and coronaries: from plaques to genes to statins. Cell 161 , 161–172 (2015). Article ADS CAS PubMed PubMed Central Google Scholar Luo, J., Yang, H. & Song, B. L. Mechanisms and regulation of cholesterol homeostasis. Nat. Rev. Mol. Cell Biol. 21 , 225–245 (2020). Article CAS PubMed Google Scholar Applebaum-Bowden, D. et al. Down-regulation of the low-density lipoprotein receptor by dietary cholesterol. Am. J. Clin. Nutr. 39 , 360–367 (1984). Article CAS PubMed Google Scholar Feingold, K. R. et al. in Endo text (eds K. R. Feingold et al.) https://www.ncbi.nlm.nih.gov/books/NBK570127/ (National Library of Medicine, 2000). Horton, J. D., Cuthbert, J. A. & Spady, D. K. Dietary fatty acids regulate hepatic low density lipoprotein (LDL) transport by altering LDL receptor protein and mRNA levels. J. Clin. Invest. 92 , 743–749 (1993). Article CAS PubMed PubMed Central Google Scholar Lecerf, J. M. & de Lorgeril, M. Dietary cholesterol: from physiology to cardiovascular risk. Br. J. Nutr. 106 , 6–14 (2011). Article CAS PubMed Google Scholar Silverman, M. G. et al. Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis. J. Am. Med. Assoc. 316 , 1289–1297 (2016). Article CAS Google Scholar Horton, J. D., Cohen, J. C. & Hobbs, H. H. Molecular biology of PCSK9: its role in LDL metabolism. Trends Biochem. Sci. 32 , 71–77 (2007). …