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Enterically derived high-density lipoprotein restrains liver injury through the portal vein.


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.

SUBMITTER: Han YH 

PROVIDER: S-EPMC8478306 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Enterically derived high-density lipoprotein restrains liver injury through the portal vein.

Han Yong-Hyun YH   Onufer Emily J EJ   Huang Li-Hao LH   Sprung Robert W RW   Davidson W Sean WS   Czepielewski Rafael S RS   Wohltmann Mary M   Sorci-Thomas Mary G MG   Warner Brad W BW   Randolph Gwendalyn J GJ  

Science (New York, N.Y.) 20210701 6553


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 HDL<sub>3</sub> subspecies form, in complex with lipopolysaccharide (LPS)-binding protein (LBP). HDL<sub>3</sub>, but not HDL<sub>2</sub> or low-density lipoprotein, prevented LPS binding to and inflammatory activa  ...[more]

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