Effects of angiopoietin-like protein 3 deficiency on postprandial lipid and lipoprotein metabolism1[S]

• Published in: Journal of lipid research Vol. 57; no. 6; pp. 1097 - 1107
• Main Authors: Minicocci, Ilenia, Tikka, Anna, Poggiogalle, Eleonora, Metso, Jari, Montali, Anna, Ceci, Fabrizio, Labbadia, Giancarlo, Fontana, Mario, Di Costanzo, Alessia, Maranghi, Marianna, Rosano, Aldo, Ehnholm, Christian, Donini, Lorenzo Maria, Jauhiainen, Matti, Arca, Marcello
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.06.2016; Elsevier
• Subjects: familial combined hypolipidemia; free fatty acids; postprandial lipid metabolism; free fatty acids; postprandial lipid metabolism; familial combined hypolipidemia
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1194/jlr.P066183

The consequences of angiopoietin-like protein 3 (ANGPTL3) deficiency on postprandial lipid and lipoprotein metabolism has not been investigated in humans. We studied 7 homozygous (undetectable circulating ANGPTL3 levels) and 31 heterozygous (50% of circulating ANGPTL3 levels) subjects with familial combined hypolipidemia (FHBL2) due to inactivating ANGPTL3 mutations in comparison with 35 controls. All subjects were evaluated at fasting and during 6 h after a high fat meal. Postprandial lipid and lipoprotein changes were quantified by calculating the areas under the curve (AUCs) using the 6 h concentration data. Plasma changes of β-hydroxybutyric acid (β-HBA) were measured as marker of hepatic oxidation of fatty acids. Compared with controls, homozygotes showed lower incremental AUCs (iAUCs) of total TG (−69%, P < 0.001), TG-rich lipoproteins (−90%, P < 0.001), apoB-48 (−78%, P = 0.032), and larger absolute increase of FFA (128%, P < 00.1). Also, heterozygotes displayed attenuated postprandial lipemia, but the difference was significant only for the iAUC of apoB-48 (−28%; P < 0.05). During the postprandial period, homozygotes, but not heterozygotes, showed a lower increase of β-HBA. Our findings demonstrate that complete ANGPTL3 deficiency associates with highly reduced postprandial lipemia probably due to faster catabolism of intestinally derived lipoproteins, larger expansion of the postprandial FFA pool, and decreased influx of dietary-derived fatty acids into the liver. These results add information on mechanisms underlying hypolipidemia in FHBL2.