{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:02:23Z","timestamp":1790229743153,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Intern Med"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Angiopoietin\u2010like protein 3 (ANGPTL3) is a key circulating regulator of triglyceride metabolism and a promising pharmacological target. The physiological consequences of profound ANGPTL3 deficiency can be explored in individuals with inherited loss\u2010of\u2010function (LOF) variants, who show reduced lifetime risk of atherosclerotic cardiovascular disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      ApoB48, apoB100 and TG metabolism were investigated in chylomicrons, VLDL1, VLDL2, IDL and LDL in 3\n                      <jats:italic>ANGPTL3<\/jats:italic>\n                      LOF homozygotes (undetectable plasma ANGPTL3), 4 LOF heterozygotes (ANGPTL3 45.0\u00a0\u00b1\u00a07.4\u00a0ng\/mL) and 10 matched controls (ANGPTL3 110.5\u00a0\u00b1\u00a027.6\u00a0ng\/mL). Studies were performed under post\u2010prandial conditions to comprehensively characterize TG transport and apoB\u2010containing lipoprotein kinetics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Chylomicron and very\u2010low\u2010density lipoproteins (VLDL) production rates were similar in ANGPTL3\u2010deficient subjects and controls. The defining abnormality in LOF homozygotes was the extremely rapid lipolysis of chylomicrons and VLDL, with circulating residence times of minutes rather than hours and accelerated conversion of VLDL to IDL and LDL. LDL particles in LOF homozygotes were TG\u2010enriched, cholesterol\u2010depleted, metabolically heterogeneous and cleared more rapidly than in controls or LOF heterozygotes. LOF heterozygotes showed a less pronounced increase in chylomicron and VLDL lipolysis, with normal IDL and LDL kinetics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Complete loss of ANGPTL3 results in a rapid acceleration of the triglyceride\u2010rich lipoprotein lipolysis pathway and promotes the formation of metabolically and compositionally abnormal LDL with accelerated clearance. These findings provide mechanistic insight into ANGPTL3 deficiency and are directly relevant for the development and safety assessment of ANGPTL3\u2010targeted therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/joim.70124","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T10:01:50Z","timestamp":1781172110000},"page":"312-328","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Angiopoietin\u2010like protein 3 complete and partial deficiency markedly accelerates apolipoprotein B48 and B100 metabolism in triglyceride\u2010rich lipoproteins in humans"],"prefix":"10.1111","volume":"300","author":[{"given":"Marcello","family":"Arca","sequence":"first","affiliation":[{"name":"Department of Translational and Precision Medicine Sapienza University of Rome  Rome 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