Apolipoprotein F is reduced in humans with steatosis and controls plasma triglyceride-rich lipoprotein metabolism.

Autor:	Deprince A; Univ. Lille , Inserm , CHU Lille , Institut Pasteur de Lille , U1011- EGID , Lille , France., Hennuyer N; Univ. Lille , Inserm , CHU Lille , Institut Pasteur de Lille , U1011- EGID , Lille , France., Kooijman S; Division of Endocrinology, and Einthoven Laboratory for Experimental Vascular Medicine , Department of Medicine , Leiden University Medical Center , Leiden , The Netherlands., Pronk ACM; Division of Endocrinology, and Einthoven Laboratory for Experimental Vascular Medicine , Department of Medicine , Leiden University Medical Center , Leiden , The Netherlands., Baugé E; Univ. Lille , Inserm , CHU Lille , Institut Pasteur de Lille , U1011- EGID , Lille , France., Lienard V; Univ. Lille , Inserm , CHU Lille , Institut Pasteur de Lille , U1011- EGID , Lille , France., Verrijken A; Department of Endocrinology, Diabetology and Metabolism , Antwerp University Hospital , Antwerp , Belgium.; Laboratory of Experimental Medicine and Paediatrics , University of Antwerp , Antwerp , Belgium., Dirinck E; Department of Endocrinology, Diabetology and Metabolism , Antwerp University Hospital , Antwerp , Belgium.; Laboratory of Experimental Medicine and Paediatrics , University of Antwerp , Antwerp , Belgium., Vonghia L; Department of Gastroenterology Hepatology , Antwerp University Hospital , Antwerp , Belgium.; Laboratory of Experimental Medicine and Paediatrics , University of Antwerp , Antwerp , Belgium., Woitrain E; Univ. Lille , Inserm , CHU Lille , Institut Pasteur de Lille , U1011- EGID , Lille , France., Kloosterhuis NJ; Department of Paediatrics , University of Groningen , University Medical Center Groningen , Groningen , The Netherlands., Marez E; Univ. Lille , Inserm , CHU Lille , Institut Pasteur de Lille , U1011- EGID , Lille , France., Jacquemain P; Univ. Lille , Inserm , CHU Lille , Institut Pasteur de Lille , U1011- EGID , Lille , France., Wolters JC; Department of Paediatrics , University of Groningen , University Medical Center Groningen , Groningen , The Netherlands., Lalloyer F; Univ. Lille , Inserm , CHU Lille , Institut Pasteur de Lille , U1011- EGID , Lille , France., Eberlé D; Univ. Lille , Inserm , CHU Lille , Institut Pasteur de Lille , U1011- EGID , Lille , France., Quemener S; Univ. Lille , Inserm , CHU Lille , Institut Pasteur de Lille , U1011- EGID , Lille , France., Vallez E; Univ. Lille , Inserm , CHU Lille , Institut Pasteur de Lille , U1011- EGID , Lille , France., Tailleux A; Univ. Lille , Inserm , CHU Lille , Institut Pasteur de Lille , U1011- EGID , Lille , France., Kouach M; Univ. Lille , CHU Lille , ULR 7365-GRITA-Groupe de Recherche sur les formes Injectables et les Technologies Associées , Lille , France., Goossens JF; Univ. Lille , CHU Lille , ULR 7365-GRITA-Groupe de Recherche sur les formes Injectables et les Technologies Associées , Lille , France., Raverdy V; Univ. Lille , Inserm, CHU Lille, Institut Pasteur de Lille , U1190 - EGID , Lille , France., Derudas B; Univ. Lille , Inserm , CHU Lille , Institut Pasteur de Lille , U1011- EGID , Lille , France., Kuivenhoven JA; Department of Paediatrics , University of Groningen , University Medical Center Groningen , Groningen , The Netherlands., Croyal M; Université de Nantes , CNRS, INSERM, l'institut du thorax , Nantes , France.; Université de Nantes , CHU Nantes, Inserm, CNRS, SFR Santé, Inserm UMS 016 , CNRS UMS 3556 , Nantes , France.; CRNH-Ouest Mass Spectrometry Core Facility , Nantes , France., van de Sluis B; Department of Paediatrics , University of Groningen , University Medical Center Groningen , Groningen , The Netherlands., Francque S; Department of Gastroenterology Hepatology , Antwerp University Hospital , Antwerp , Belgium.; Laboratory of Experimental Medicine and Paediatrics , University of Antwerp , Antwerp , Belgium., Pattou F; Univ. Lille , Inserm, CHU Lille, Institut Pasteur de Lille , U1190 - EGID , Lille , France., Rensen PCN; Division of Endocrinology, and Einthoven Laboratory for Experimental Vascular Medicine , Department of Medicine , Leiden University Medical Center , Leiden , The Netherlands., Staels B; Univ. Lille , Inserm , CHU Lille , Institut Pasteur de Lille , U1011- EGID , Lille , France., Haas JT; Univ. Lille , Inserm , CHU Lille , Institut Pasteur de Lille , U1011- EGID , Lille , France.
Jazyk:	angličtina
Zdroj:	Hepatology (Baltimore, Md.) [Hepatology] 2023 Apr 01; Vol. 77 (4), pp. 1287-1302. Date of Electronic Publication: 2022 Jul 15.
DOI:	10.1002/hep.32631
Abstrakt:	Background: NAFLD affects nearly 25% of the global population. Cardiovascular disease (CVD) is the most common cause of death among patients with NAFLD, in line with highly prevalent dyslipidemia in this population. Increased plasma triglyceride (TG)-rich lipoprotein (TRL) concentrations, an important risk factor for CVD, are closely linked with hepatic TG content. Therefore, it is of great interest to identify regulatory mechanisms of hepatic TRL production and remnant uptake in the setting of hepatic steatosis. Approach and Results: To identify liver-regulated pathways linking intrahepatic and plasma TG metabolism, we performed transcriptomic analysis of liver biopsies from two independent cohorts of obese patients. Hepatic encoding apolipoprotein F ( APOF ) expression showed the fourth-strongest negatively correlation with hepatic steatosis and the strongest negative correlation with plasma TG levels. The effects of adenoviral-mediated human ApoF (hApoF) overexpression on plasma and hepatic TG were assessed in C57BL6/J mice. Surprisingly, hApoF overexpression increased both hepatic very low density lipoprotein (VLDL)-TG secretion and hepatic lipoprotein remnant clearance, associated a ~25% reduction in plasma TG levels. Conversely, reducing endogenous ApoF expression reduced VLDL secretion in vivo , and reduced hepatocyte VLDL uptake by ~15% in vitro . Transcriptomic analysis of APOF -overexpressing mouse livers revealed a gene signature related to enhanced ApoB-lipoprotein clearance, including increased expression of Ldlr and Lrp1 , among others. Conclusion: These data reveal a previously undescribed role for ApoF in the control of plasma and hepatic lipoprotein metabolism by favoring VLDL-TG secretion and hepatic lipoprotein remnant particle clearance. (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)
Databáze:	MEDLINE
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