Hepatic scavenger receptor class B, type I is stimulated by peroxisome proliferator-activated receptor γ and hepatocyte nuclear factor 4α

• Published in: Biochemical and biophysical research communications Vol. 305; no. 3; pp. 557 - 565
• Main Authors: Malerød, Lene, Sporstøl, Marita, Juvet, Lene K., Mousavi, Ali, Gjøen, Tor, Berg, Trond
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 06.06.2003
• Subjects: Gene regulation; HNF4; Liver; PPAR; SR-BI; SR-BI; PPAR; HNF4; Gene regulation; Liver
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/S0006-291X(03)00819-2

Excessive cellular cholesterol is transported to the liver by a pathway called ‘reverse cholesterol transport.’ Scavenger receptor class B, type I (SR-BI) mediates cholesterol uptake in the liver. Polyunsaturated fatty acids, known to activate peroxisome proliferator-activated receptor (PPAR), have been reported to increase hepatic cholesterol uptake. We found in the present study that PPARγ induces expression of SR-BI in rat hepatocytes, liver endothelial cells, and Kupffer cells. In contrast, PPARα increased SR-BI levels only in hepatocytes and liver endothelial cells. PPARγ/RXR binds to a response element between −459 and −472 bp in the human SR-BI promoter. Furthermore, hepatocyte nuclear factor 4α (HNF4α) was found to enhance PPARγ-mediated SR-BI transcription. Thiazolidinedione (TZD)-activated PPARγ/RXR increased hepatic SR-BI levels, which may lead to increased hepatic cholesterol uptake and less accumulation of lipids in peripheral tissues. The present results are in agreement with previous reports, indicating that specific PPARγ-agonists (such as TZDs) protect against atherosclerosis.