Enterically derived high-density lipoprotein restrains liver injury through the portal vein
Top Cited Papers
- 22 July 2021
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 373 (6553), 410-+
- https://doi.org/10.1126/science.abe6729
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.Keywords
Funding Information
- National Institutes of Health (DP1DK1109668)
- National Institutes of Health (AI0499653)
- National Institutes of Health (T32 DK077653)
- National Institutes of Health (NIH RO1 HL127649)
- National Institutes of Health (HL138908)
- National Institutes of Health (P30 DK052574)
- National Institutes of Health (NIGMS P41 GM103422)
- National Institutes of Health (R24GM136766)
- NIH Office of the Director (DP1DK1109668)
- Norsk Revmatikerforbund (NIH T32DK077653)
- NIH (NIH R01 DK119147)
- NIH (DP1DK1109668)
- NIH (AI0499653)
- NIH (NIH RO1 HL127649)
- NIH (HL138908)
- NIH Office of the Director (AI0499653)
- National Institutes of Health (DK119147)
- NIH Office of the Director (T32 DK077653)
- work (NIH R01DK119147)
- work (AI0499653)
- Lawrence Pakula MD IBD Research Fellowship (NIH RO1HL127649)
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