| First Author | Lee SX | Year | 2018 |
| Journal | J Clin Invest | Volume | 128 |
| Issue | 4 | Pages | 1615-1626 |
| PubMed ID | 29408809 | Mgi Jnum | J:261175 |
| Mgi Id | MGI:6154424 | Doi | 10.1172/JCI94230 |
| Citation | Lee SX, et al. (2018) FoxO transcription factors are required for hepatic HDL cholesterol clearance. J Clin Invest 128(4):1615-1626 |
| abstractText | Insulin resistance and type 2 diabetes are associated with low levels of high-density lipoprotein cholesterol (HDL-C). The insulin-repressible FoxO transcription factors are potential mediators of the effect of insulin on HDL-C. FoxOs mediate a substantial portion of insulin-regulated transcription, and poor FoxO repression is thought to contribute to the excessive glucose production in diabetes. In this work, we show that mice with liver-specific triple FoxO knockout (L-FoxO1,3,4), which are known to have reduced hepatic glucose production, also have increased HDL-C. This was associated with decreased expression of the HDL-C clearance factors scavenger receptor class B type I (SR-BI) and hepatic lipase and defective selective uptake of HDL cholesteryl ester by the liver. The phenotype could be rescued by re-expression of SR-BI. These findings demonstrate that hepatic FoxOs are required for cholesterol homeostasis and HDL-mediated reverse cholesterol transport to the liver. |
