Faculty Collaboration Database

Enterically derived high-density lipoprotein restrains liver injury through the portal vein. Science 2021 Jul 23;373(6553)

Date

08/27/2021

Pubmed ID

34437091

Pubmed Central ID

PMC8478306

DOI

10.1126/science.abe6729

Scopus ID

2-s2.0-85111031761 (requires institutional sign-in at Scopus site)   90 Citations

Abstract

The biogenesis of high-density lipoprotein (HDL) requires apoA1 and the cholesterol transporter ABCA1. Although the liver generates most of the HDL in the blood, HDL synthesis also occurs in the small intestine. Here, we show that intestine-derived HDL traverses the portal vein in the HDL₃ subspecies form, in complex with lipopolysaccharide (LPS)-binding protein (LBP). HDL₃, but not HDL₂ or low-density lipoprotein, prevented LPS binding to and inflammatory activation of liver macrophages and instead supported extracellular inactivation of LPS. In mouse models involving surgical, dietary, or alcoholic intestinal insult, loss of intestine-derived HDL worsened liver injury, whereas outcomes were improved by therapeutics that elevated and depended upon raising intestinal HDL. Thus, protection of the liver from injury in response to gut-derived LPS is a major function of intestinally synthesized HDL.

Author List

Han YH, Onufer EJ, Huang LH, Sprung RW, Davidson WS, Czepielewski RS, Wohltmann M, Sorci-Thomas MG, Warner BW, Randolph GJ

Author

Mary Sorci Thomas PhD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute-Phase Proteins
Adult
Animals
Carrier Proteins
Cholesterol, HDL
Enterocytes
Humans
Intestine, Small
Kupffer Cells
Lipopolysaccharide Receptors
Lipopolysaccharides
Lipoproteins, HDL3
Liver
Liver Cirrhosis
Liver Diseases
Liver X Receptors
Membrane Glycoproteins
Mice
Mice, Inbred C57BL
Portal Vein
Protein Binding
Signal Transduction
Toll-Like Receptor 4