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

Hennuyer, Nathalie; Kooijman, Sander; Pronk, Amanda; Baugé, Eric; Liénard, Viktor; Verrijken, An; Dirinck, Eveline; Vonghia, Luisa; Woitrain, Eloïse; Kloosterhuis, Niels J.; Marez, Eléonore; Jacquemain, Pauline; Wolters, Justina C.; Lalloyer, Fanny; Eberlé, Delphine; Quemener, Sandrine; Vallez, Emmanuelle; Tailleux, Anne; Kouach, Mostafa; Goossens, Jean‐François; Raverdy, Violeta; Derudas, Bruno; Kuivenhoven, Jan Albert; Croyal, Mikaël; Sluis, Bart van de; Francque, Sven; Pattou, François; Rensen, Patrick C.N.; Staels, Bart; Haas, Joel T.

doi:10.1002/hep.32631

Cited by 8 publications

(3 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Apolipoproteins assemble in the ER, and thus TAG accumulation can induce ER stress and the inhibition of APOB synthesis [40]. The lower expression of APOB could contribute to the steatosis in Pi*ZZ AATD patients, as it has been similarly described for APOA1 and APOF in NAFLD [41,42]. Hence, altered lipoprotein transport and secretion, mirrored by the reduced expression of APOB and/or FABP1, and increased expression of CD36 may, at least in part, explain the accumulation of lipids in Pi*ZZ liver.…”

Section: Discussionmentioning

confidence: 91%

Quantitative Lipid Profiling Reveals Major Differences between Liver Organoids with Normal PiM and Deficient PiZ Variants of Alpha-1-antitrypsin

Pérez-Luz,

Lalchandani,

Matamala

et al. 2023

IJMS

View full text Add to dashboard Cite

Different mutations in the SERPINA1 gene result in alpha-1 antitrypsin (AAT) deficiency and in an increased risk for the development of liver diseases. More than 90% of severe deficiency patients are homozygous for Z (Glu342Lys) mutation. This mutation causes Z-AAT polymerization and intrahepatic accumulation which can result in hepatic alterations leading to steatosis, fibrosis, cirrhosis, and/or hepatocarcinoma. We aimed to investigate lipid status in hepatocytes carrying Z and normal M alleles of the SERPINA1 gene. Hepatic organoids were developed to investigate lipid alterations. Lipid accumulation in HepG2 cells overexpressing Z-AAT, as well as in patient-derived hepatic organoids from Pi*MZ and Pi*ZZ individuals, was evaluated by Oil-Red staining in comparison to HepG2 cells expressing M-AAT and liver organoids from Pi*MM controls. Furthermore, mass spectrometry-based lipidomics analysis and transcriptomic profiling were assessed in Pi*MZ and Pi*ZZ organoids. HepG2 cells expressing Z-AAT and liver organoids from Pi*MZ and Pi*ZZ patients showed intracellular accumulation of AAT and high numbers of lipid droplets. These latter paralleled with augmented intrahepatic lipids, and in particular altered proportion of triglycerides, cholesterol esters, and cardiolipins. According to transcriptomic analysis, Pi*ZZ organoids possess many alterations in genes and cellular processes of lipid metabolism with a specific impact on the endoplasmic reticulum, mitochondria, and peroxisome dysfunction. Our data reveal a relationship between intrahepatic accumulation of Z-AAT and alterations in lipid homeostasis, which implies that liver organoids provide an excellent model to study liver diseases related to the mutation of the SERPINA1 gene.

show abstract

Section: Discussionmentioning

confidence: 91%

Quantitative Lipid Profiling Reveals Major Differences between Liver Organoids with Normal PiM and Deficient PiZ Variants of Alpha-1-antitrypsin

Pérez-Luz,

Lalchandani,

Matamala

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…In organisms, cholesterol and triglycerides (TGs) are the primary lipids that are insoluble in water and need to bind with circulating plasma apolipoproteins (Apos) to form lipoproteins, thus enabling the transportation and metabolism of lipids [ 2 ]. The liver is the central organ responsible for lipid metabolism due to its involvement in the synthesis of lipoproteins for lipid transportation as well as fat synthesis and breakdown [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Unveiling the Impact of ApoF Deficiency on Liver and Lipid Metabolism: Insights from Transcriptome-Wide m6A Methylome Analysis in Mice

Shen,

Chen,

Zhang

et al. 2024

Genes

View full text Add to dashboard Cite

Lipid metabolism participates in various physiological processes and has been shown to be connected to the development and progression of multiple diseases, especially metabolic hepatopathy. Apolipoproteins (Apos) act as vectors that combine with lipids, such as cholesterol and triglycerides (TGs). Despite being involved in lipid transportation and metabolism, the critical role of Apos in the maintenance of lipid metabolism has still not been fully revealed. This study sought to clarify variations related to m6A methylome in ApoF gene knockout mice with disordered lipid metabolism based on the bioinformatics method of transcriptome-wide m6A methylome epitranscriptomics. High-throughput methylated RNA immunoprecipitation sequencing (MeRIP-seq) was conducted in both wild-type (WT) and ApoF knockout (KO) mice. As a result, the liver histopathology presented vacuolization and steatosis, and the serum biochemical assays reported abnormal lipid content in KO mice. The m6A-modified mRNAs were conformed consensus sequenced in eukaryotes, and the distribution was enriched within the coding sequences and 3′ non-coding regions. In KO mice, the functional annotation terms of the differentially expressed genes (DEGs) included cholesterol, steroid and lipid metabolism, and lipid storage. In the differentially m6A-methylated mRNAs, the functional annotation terms included cholesterol, TG, and long-chain fatty acid metabolic processes; lipid transport; and liver development. The overlapping DEGs and differential m6A-modified mRNAs were also enriched in terms of lipid metabolism disorder. In conclusion, transcriptome-wide MeRIP sequencing in ApoF KO mice demonstrated the role of this crucial apolipoprotein in liver health and lipid metabolism.

show abstract

“…The apolipoprotein F (APOF) gene is located at 12q13.3, and its product was identified as a minor apolipoprotein in plasma first in 1978, which may be involved in cholesterol (CE) transport and/or esterification [ 1 ]. APOF was found to be expressed at a considerable higher level in normal liver than in other parts of human organs, mainly participating in lipoprotein metabolism [ 2 , 3 ]. APOF inhibits cholesteryl ester transfer protein (CETP) activity, among which it preferentially inhibits transfer events involving low-density lipoprotein (LDL) [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

A pan-cancer analysis of the oncogenic and immunological roles of apolipoprotein F (APOF) in human cancer

Shi

Feng

et al. 2023

Eur J Med Res

View full text Add to dashboard Cite

Background Apolipoprotein F (APOF) has been less studied in cancers. Thus, we aimed to perform a pan-cancer analysis of the oncogenic and immunological effects of APOF on human cancer. Methods A standardized TCGA pan-cancer dataset was downloaded. Differential expression, clinical prognosis, genetic mutations, immune infiltration, epigenetic modifications, tumor stemness and heterogeneity were analyzed. We conducted all analyses through software R (version 3.6.3) and its suitable packages. Results Overall, we found that the common cancers differentially expressed between tumor and normal samples and prognostic-associated were BRCA, PRAD, KIRP, and LIHC in terms of overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS). The pan-cancer Spearman analysis showed that the mRNA expression of APOF was negatively correlated with four tumor stemness indexes (DMPss, DNAss, ENHss, and EREG-METHss) with statistical significance for PRAD and was positively correlated for LIHC. In terms of BRCA and PRAD patients, we found negative correlation of APOF with TMB, MSI, neo, HRD and LOH. The mutation frequencies of BRCA and LIHC were 0.3%. APOF expression was negatively correlated with immune infiltration and positively correlated with tumor purity for PRAD patients. The mRNA expression of APOF was negatively associated with most TILs for LIHC, B cells, CD4+ T cells, neutrophils, macrophages and dendritic cells, but was positively associated with CD8+ T cells. Conclusions Our pan-cancer study offered a relatively comprehensive understanding of the roles of APOF on BRCA, PRAD, KIRP, and LIHC.

show abstract

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

Cited by 8 publications

References 46 publications

Quantitative Lipid Profiling Reveals Major Differences between Liver Organoids with Normal PiM and Deficient PiZ Variants of Alpha-1-antitrypsin

Quantitative Lipid Profiling Reveals Major Differences between Liver Organoids with Normal PiM and Deficient PiZ Variants of Alpha-1-antitrypsin

Unveiling the Impact of ApoF Deficiency on Liver and Lipid Metabolism: Insights from Transcriptome-Wide m6A Methylome Analysis in Mice

A pan-cancer analysis of the oncogenic and immunological roles of apolipoprotein F (APOF) in human cancer

Contact Info

Product

Resources

About

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

Cited by 8 publications

References 46 publications

Quantitative Lipid Profiling Reveals Major Differences between Liver Organoids with Normal Pi*M and Deficient Pi*Z Variants of Alpha-1-antitrypsin

Quantitative Lipid Profiling Reveals Major Differences between Liver Organoids with Normal Pi*M and Deficient Pi*Z Variants of Alpha-1-antitrypsin

Unveiling the Impact of ApoF Deficiency on Liver and Lipid Metabolism: Insights from Transcriptome-Wide m6A Methylome Analysis in Mice

A pan-cancer analysis of the oncogenic and immunological roles of apolipoprotein F (APOF) in human cancer

Contact Info

Product

Resources

About

Quantitative Lipid Profiling Reveals Major Differences between Liver Organoids with Normal PiM and Deficient PiZ Variants of Alpha-1-antitrypsin

Quantitative Lipid Profiling Reveals Major Differences between Liver Organoids with Normal PiM and Deficient PiZ Variants of Alpha-1-antitrypsin