title: Effects of angiopoietin-like protein 3 deficiency on postprandial lipid and lipoprotein metabolism.
abstract: 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.
authors.affiliation: Departments of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy.
authors.forename: Ilenia
authors.initials: I
authors.lastname: Minicocci
authors.affiliation: National Institute for Health and Welfare, Genomics and Biomarkers Unit, Biomedicum, Helsinki, Finland.
authors.forename: Anna
authors.initials: A
authors.lastname: Tikka
authors.affiliation: Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Poggiogalle
authors.affiliation: National Institute for Health and Welfare, Genomics and Biomarkers Unit, Biomedicum, Helsinki, Finland.
authors.forename: Jari
authors.initials: J
authors.lastname: Metso
authors.affiliation: Departments of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Montali
authors.affiliation: Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Ceci
authors.affiliation: Departments of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Labbadia
authors.affiliation: Departments of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Fontana
authors.affiliation: Departments of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Di Costanzo
authors.affiliation: Departments of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Maranghi
authors.affiliation: ISFOL, Department of Employment and Social Policies, Rome, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Rosano
authors.affiliation: National Institute for Health and Welfare, Genomics and Biomarkers Unit, Biomedicum, Helsinki, Finland.
authors.forename: Christian
authors.initials: C
authors.lastname: Ehnholm
authors.affiliation: Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Lorenzo Maria
authors.initials: LM
authors.lastname: Donini
authors.affiliation: National Institute for Health and Welfare, Genomics and Biomarkers Unit, Biomedicum, Helsinki, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Jauhiainen
authors.affiliation: Departments of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy marcello.arca@uniroma1.it.
authors.forename: Marcello
authors.identifier: 0000-0003-3786-0883
authors.initials: M
authors.lastname: Arca
mesh_terms: D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000097:blood / Q000172:deficiency / Q000235:genetics*; D053283:Apolipoprotein B-48 / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006995:Hypobetalipoproteinemias / Q000097:blood* / Q000235:genetics / Q000473:pathology; D008055:Lipids / Q000097:blood*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019518:Postprandial Period; D014280:Triglycerides / Q000097:blood
chemical_list: C479896:ANGPTL3 protein, human; D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D053283:Apolipoprotein B-48; D005230:Fatty Acids, Nonesterified; D008055:Lipids; D008074:Lipoproteins; D014280:Triglycerides
keywords: familial combined hypolipidemia; free fatty acids; postprandial lipid metabolism