Streptococcal serum opacity factor promotes cholesterol ester metabolism and bile acid secretion in vitro and in vivo

Baiba K. Gillard, Perla J. Rodriguez, David W. Fields, Joe L. Raya, William R. Lagor, Corina Rosales, Harry S. Courtney, Antonio M. Gotto, Henry J. Pownall

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Plasma high density lipoprotein-cholesterol (HDL-C) concentrations negatively correlate with atherosclerotic cardiovascular disease. HDL is thought to have several atheroprotective functions, which are likely distinct from the epidemiological inverse relationship between HDL-C levels and risk. Specifically, strategies that reduce HDL-C while promoting reverse cholesterol transport (RCT) may have therapeutic value. The major product of the serum opacity factor (SOF) reaction versus HDL is a cholesteryl ester (CE)-rich microemulsion (CERM), which contains apo E and the CE of ~ 400,000 HDL particles. Huh7 hepatocytes take up CE faster when delivered as CERM than as HDL, in part via the LDL-receptor (LDLR). Here we compared the final RCT step, hepatic uptake and subsequent intracellular processing to cholesterol and bile salts for radiolabeled HDL-, CERM- and LDL-CE by Huh7 cells and in vivo in C57BL/6J mice. In Huh7 cells, uptake from LDL was greater than from CERM (2-4X) and HDL (5-10X). Halftimes for [14C]CE hydrolysis were 3.0 ± 0.2, 4.4 ± 0.6 and 5.4 ± 0.7 h respectively for HDL, CERM and LDL-CE. The fraction of sterols secreted as bile acids was ~ 50% by 8 h for all three particles. HDL, CERM and LDL-CE metabolism in mice showed efficient plasma clearance of CERM-CE, liver uptake and metabolism, and secretion as bile acids into the gall bladder. This work supports the therapeutic potential of the SOF reaction, which diverts HDL-CE to the LDLR, thereby increasing hepatic CE uptake, and sterol disposal as bile acids.

Original languageEnglish (US)
Pages (from-to)196-204
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1861
Issue number3
DOIs
StatePublished - Mar 1 2016

Keywords

  • Bile acid secretion
  • Cholesterol ester metabolism
  • HDL function
  • Huh7 human hepatocytes
  • Reverse cholesterol transport
  • Serum opacity factor

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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