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LIPIDS

ASGR1 inhibition stimulates cholesterol excretion

Nature Reviews Cardiology volume 19, page 642 (2022)Cite this article

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Inhibition of asialoglycoprotein receptor 1 (ASGR1), a liver-specific receptor that promotes the endocytosis and lysosomal degradation of glycoproteins, reduces plasma lipid levels by promoting cholesterol excretion. This finding, published in Nature, reveals a novel mechanism that can be targeted to reduce cholesterol in patients who are already receiving cholesterol-lowering drugs.

To delineate the metabolic pathways involved in the cholesterol-lowering effects of ASGR1, Bao-Liang Song and colleagues generated ASGR1-deficient mice. Compared with wild-type mice, Asgr1−/− mice had significantly lower serum total cholesterol and triglycerides, as well as increased concentrations of biliary cholesterol and bile acids in the gallbladder. Furthermore, these mice had increased levels of LXRα in the liver, as well as an increase in the expression of ABCA1 and ABCG5/ABCG8, which mediate cholesterol transport to HDL and excretion to bile and faeces, respectively. The investigators confirmed that the metabolic improvements observed in Asgr1−/− mice were dependent on LXRα, as the lipid changes induced by Asgr1 knockout were abrogated by Lxra ablation.

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  1. Nature Reviews Cardiology http://www.nature.com/nrcardio/

    Karina Huynh

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  1. Karina Huynh
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Correspondence to Karina Huynh.

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Huynh, K. ASGR1 inhibition stimulates cholesterol excretion. Nat Rev Cardiol 19, 642 (2022). https://doi.org/10.1038/s41569-022-00768-9

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