Details

Autor(en) / Beteiligte

• Lee, Samuel X
• Heine, Markus
• Schlein, Christian
• Ramakrishnan, Rajasekhar
• Liu, Jing
• Belnavis, Gabriella
• Haimi, Ido
• Fischer, Alexander W
• Ginsberg, Henry N
• Heeren, Joerg
• Rinninger, Franz
• Haeusler, Rebecca A

Titel

FoxO transcription factors are required for hepatic HDL cholesterol clearance

Ist Teil von

• The Journal of clinical investigation, 2018-04, Vol.128 (4), p.1615-1626

Ort / Verlag

United States: American Society for Clinical Investigation

Erscheinungsjahr

2018

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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.