| First Author | Han YH | Year | 2021 |
| Journal | Science | Volume | 373 |
| Issue | 6553 | PubMed ID | 34437091 |
| Mgi Jnum | J:360149 | Mgi Id | MGI:7797510 |
| Doi | 10.1126/science.abe6729 | Citation | Han YH, et al. (2021) Enterically derived high-density lipoprotein restrains liver injury through the portal vein. Science 373(6553) |
| abstractText | 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(3) subspecies form, in complex with lipopolysaccharide (LPS)-binding protein (LBP). HDL(3), but not HDL(2) 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. |
