Metabolomic Signature of Angiopoietin-Like Protein 3 Deficiency in Fasting and Postprandial State

Arteriosclerosis, Thrombosis, and Vascular Biology
Emmi TikkanenMarcello Arca

Abstract

Objective- Loss-of-function (LOF) variants in the ANGPTL3 (angiopoietin-like protein 3) have been associated with low levels of plasma lipoproteins and decreased coronary artery disease risk. We aimed to determine detailed metabolic effects of genetically induced ANGPTL3 deficiency in fasting and postprandial state. Approach and Results- We studied individuals carrying S17X LOF mutation in ANGPTL3 (6 homozygous and 32 heterozygous carriers) and 38 noncarriers. Nuclear magnetic resonance metabolomics was used to quantify 225 circulating metabolic measures. We compared metabolic differences between LOF carriers and noncarriers in fasting state and after a high-fat meal. In fasting, ANGPTL3 deficiency was characterized by similar extent of reductions in LDL (low-density lipoprotein) cholesterol (0.74 SD units lower concentration per LOF allele [95% CI, 0.42-1.06]) as observed for many TRL (triglyceride-rich lipoprotein) measures, including VLDL (very-low-density lipoprotein) cholesterol (0.75 [95% CI, 0.45-1.05]). Within most lipoprotein subclasses, absolute levels of cholesterol were decreased more than triglycerides, resulting in the relative proportion of cholesterol being reduced within TRLs and their remnants. Further, β-hydr...Continue Reading

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Citations

Feb 6, 2020·Current Opinion in Lipidology·Marcello ArcaIlenia Minicocci
Jun 25, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Harsh AgrawalMichelle A Albert
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Mar 8, 2021·Molecular Biology Reports·Xin Su
Aug 11, 2020·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Hanna RuhanenVesa M Olkkonen
May 29, 2021·Diabetes, Obesity & Metabolism·Ping LingJianping Weng
Jul 25, 2021·International Journal of Molecular Sciences·Pei-Yi ChenJui-Hung Yen

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