Scavenger receptor BI facilitates hepatic very low density lipoprotein production in mice

Harmen Wiersma, Niels Nijstad, Thomas Gautier, Jahangir Iqbal, Folkert Kuipers, M. Mahmood Hussain, Uwe J. F. Tietge*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

26 Citations (Scopus)

Abstract

Scavenger receptor BI (SR-BI) is a selective uptake receptor for HDL cholesterol but is also involved in the catabolism of apolipoprotein (apo)B-containing lipoproteins. However, plasma levels of apoB-containing lipoproteins increase following hepatic SR-BI overexpression, suggesting that SR-BI not solely mediates their catabolism. We therefore tested the hypothesis that hepatic SR-BI impacts on VLDL production. On day 7 following adenovirus (Ad)-mediated overexpression of SR-BI, VLDL-triglyceride and VLDL-apoB production rates were significantly increased (P <0.001), whereas VLDL production was significantly lower in SR-BI knockout mice compared with controls (P <0.05). In mice injected with AdSR-BI, hepatic cholesterol content increased (P <0.001), microsomal triglyceride transfer protein activity was higher (P <0.01) and expression of sterol-regulatory element binding protein (SREBP) 2 and its target genes was decreased (P <0.01). Conversely, in SR-BI knockout mice, microsomal triglyceride transfer protein activity was lower and expression of SREBP2 target genes was increased (P <0.01). Finally, we demonstrate in vitro in isolated primary hepatocytes as well as in vivo that cholesterol derived from HDL and taken up via SR-BI into the liver can be resecreted within VLDL. These data indicate that hepatic SR-BI expression is linked to VLDL production, and within liver, a metabolic shunt might exist that delivers HDL cholesterol, at least in part, to a pool from which cholesterol is mobilized for VLDL production. These results might have implications for HDL-based therapies against atherosclerotic cardiovascular disease, especially with SR-BI as target.-Wiersma, H., N. Nijstad, T. Gautier, J. Iqbal, F. Kuipers, M. M. Hussain, and U. J. F. Tietge. Scavenger receptor BI facilitates hepatic very low density lipoprotein production in mice. J. Lipid Res. 2010. 51: 544-553.

Original languageEnglish
Pages (from-to)544-553
Number of pages10
JournalJournal of Lipid Research
Volume51
Issue number3
DOIs
Publication statusPublished - Mar-2010

Keywords

  • triglycerides
  • cholesterol
  • liver
  • hepatocytes
  • labeling
  • high density lipoproteins
  • microsomal triglyceride transfer protein
  • apolipoprotein B
  • BILIARY CHOLESTEROL SECRETION
  • TRIGLYCERIDE TRANSFER PROTEIN
  • I TRANSGENIC MICE
  • SR-BI
  • DEFICIENT MICE
  • HDL CHOLESTEROL
  • APO-B
  • CHYLOMICRON METABOLISM
  • APOLIPOPROTEIN-B
  • SELECTIVE UPTAKE

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