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

被引：13

作者：

Deprince, Audrey ^{[1
]}

Hennuyer, Nathalie ^{[1
]}

Kooijman, Sander ^{[2
,3
]}

Pronk, Amanda C. M. ^{[2
,3
]}

Bauge, Eric ^{[1
]}

Lienard, Viktor ^{[1
]}

Verrijken, An ^{[4
,6
]}

Dirinck, Eveline ^{[4
,6
]}

Vonghia, Luisa ^{[5
,6
]}

Woitrain, Eloise ^{[1
]}

Kloosterhuis, Niels J. ^{[7
]}

Marez, Eleonore ^{[1
]}

Jacquemain, Pauline ^{[1
]}

Wolters, Justina C. ^{[7
]}

Lalloyer, Fanny ^{[1
]}

Eberle, Delphine ^{[1
]}

Quemener, Sandrine ^{[1
]}

Vallez, Emmanuelle ^{[1
]}

Tailleux, Anne ^{[1
]}

Kouach, Mostafa ^{[8
]}

Goossens, Jean-Francois ^{[8
]}

Raverdy, Violeta ^{[9
]}

Derudas, Bruno ^{[1
]}

Kuivenhoven, Jan Albert ^{[7
]}

Croyal, Mikael ^{[10
,11
,12
]}

van de Sluis, Bart ^{[7
]}

Francque, Sven ^{[5
,6
]}

Pattou, Francois ^{[9
]}

Rensen, Patrick C. N. ^{[2
,3
]}

Staels, Bart ^{[1
]}

Haas, Joel T. ^{[1
]}

机构：

[1] Univ Lille, CHU Lille, INSERM, Inst Pasteur Lille,U1011,EGID, Lille, France

[2] Leiden Univ, Div Endocrinol, Dept Med, Med Ctr, Leiden, Netherlands

[3] Leiden Univ, Dept Med, Einthoven Lab Expt Vasc Med, Med Ctr, Leiden, Netherlands

[4] Univ Antwerp Hosp, Dept Endocrinol Diabetol & Metab, Antwerp, Belgium

[5] Univ Antwerp Hosp, Dept Gastroenterol Hepatol, Antwerp, Belgium

[6] Univ Antwerp, Lab Expt Med & Paediat, Antwerp, Belgium

[7] Univ Groningen, Univ Med Ctr Groningen, Dept Paediat, Groningen, Netherlands

[8] Univ Lille, CHU Lille, ULR 7365, GRITA Grp Rech formes Injectables & Technol Assoc, Lille, France

[9] Univ Lille, CHU Lille, INSERM, U1190,EGID,Inst Pasteur Lille, Lille, France

[10] Univ Nantes, CNRS, INSERM, Institut Thorax, Nantes, France

[11] Univ Nantes, CHU Nantes, CNRS, SFR Sante,Inserm,UMS 3556,UMS 016, Nantes, France

[12] CRNH Ouest Mass Spectrometry Core Facil, Nantes, France

来源：

HEPATOLOGY | 2023年 / 77卷 / 04期

基金：

欧盟地平线“2020”;

关键词：

HEPARAN-SULFATE PROTEOGLYCANS; DE-NOVO LIPOGENESIS; CONFERS SUSCEPTIBILITY; DENSITY-LIPOPROTEINS; LIPID TRANSFER; OBESE MEN; LIVER; CHOLESTEROL; PROTEIN; ATHEROSCLEROSIS;

D O I：

10.1002/hep.32631

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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 similar to 25% reduction in plasma TG levels. Conversely, reducing endogenous ApoF expression reduced VLDL secretion in vivo, and reduced hepatocyte VLDL uptake by similar to 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.

引用

页码：1287 / 1302

页数：16

共 46 条

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