Angiopoietin-like protein 3, an emerging cardiometabolic therapy target with systemic and cell-autonomous functions

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Ruhanen , H , Haridas , P A N , Jauhiainen , M & Olkkonen , V M 2020 , ' Angiopoietin-like protein 3, an emerging cardiometabolic therapy target with systemic and cell-autonomous functions ' , Biochimica and Biophysica Acta. Molecular and Cell Biology of Lipids , vol. 1865 , no. 12 , 158791 . https://doi.org/10.1016/j.bbalip.2020.158791

Title: Angiopoietin-like protein 3, an emerging cardiometabolic therapy target with systemic and cell-autonomous functions
Author: Ruhanen, Hanna; Haridas, P. A. Nidhina; Jauhiainen, Matti; Olkkonen, Vesa M.
Contributor: University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, Medicum
Date: 2020-12
Language: eng
Number of pages: 10
Belongs to series: Biochimica and Biophysica Acta. Molecular and Cell Biology of Lipids
ISSN: 1388-1981
URI: http://hdl.handle.net/10138/333374
Abstract: Angiopoietin like protein 3 (ANGPTL3) is best known for its function as an inhibitor of lipoprotein and endothelial lipases. Due to the capacity of genetic or pharmacologic ANGPTL3 suppression to markedly reduce circulating lipoproteins, and the documented cardioprotection upon such suppression, ANGPTL3 has become an emerging therapy target for which both antibody and antisense oligonucleotide (ASO) therapeutics are being clinically tested. While the antibody is relatively selective for circulating ANGPTL3, the ASO also depletes the intra-hepatocellular protein, and there is emerging evidence for cell-autonomous functions of ANGPTL3 in the liver. These include regulation of hepatocyte glucose and fatty acid uptake, insulin sensitivity, LDL/VLDL remnant uptake, VLDL assembly/secretion, polyunsaturated fatty acid (PUFA) and PUFA-derived lipid mediator content, and gene expression. In this review we elaborate on (i) why ANGPTL3 is considered one of the most promising new cardiometabolic therapy targets, and (ii) the present evidences for its intra-hepatocellular or cell-autonomous functions.
Subject: Angiopoietin-like 3
Lipoprotein lipase
Lipid metabolism
Intracellular function
Hepatic lipids
Therapy target
FAMILIAL COMBINED HYPOLIPIDEMIA
LOW-DENSITY LIPOPROTEIN
PRORESOLVING LIPID MEDIATORS
FATTY LIVER
ANGPTL3 DEFICIENCY
ADIPOSE-TISSUE
PLASMA-LIPIDS
METABOLISM
HYPOBETALIPOPROTEINEMIA
GENE
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
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