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

The biogenesis of high-density lipoprotein (HDL) requires apoA1 and the ldl cholesterol transporter ABCA1. Although the liver generates most of the HDL in the blood, HDL synthesis additionally happens in the small gut. Here, we present that intestine-derived HDL traverses the portal vein in the HDL3 subspecies kind, in complicated with lipopolysaccharide (LPS)–binding protein (LBP). HDL3, however not HDL2 or low-density lipoprotein, prevented LPS binding to and inflammatory activation of liver macrophages and as a substitute supported extracellular inactivation of LPS. In mouse fashions involving surgical, dietary, or alcoholic intestinal insult, lack of intestine-derived HDL worsened liver injury, whereas outcomes had been improved by therapeutics that elevated and depended upon elevating intestinal HDL. Thus, safety of the liver from injury in response to gut-derived LPS is a serious operate of intestinally synthesized HDL.
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