The APOA1bp–SREBF–NOTCH axis is associated with reduced atherosclerosis risk in morbidly obese patients

  • Jordi Mayneris-Perxachs
    Department of Endocrinology, Diabetes and Nutrition, Hospital of Girona “Dr Josep Trueta”, Departament de Ciències Mèdiques, University of Girona, Girona Biomedical Research Institute (IdibGi), Girona, Spain

    CIBERobn Pathophysiology of Obesity and Nutrition, Instituto de Salud Carlos III, Madrid, Spain
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  • Josep Puig
    Department of Radiology, Diagnostic Imaging Institute (IDI), Dr Josep Trueta University Hospital, IDIBGI, Girona, Spain
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  • Rémy Burcelin
    Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France

    Université Paul Sabatier (UPS), Unité Mixte de Recherche (UMR) 1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Team 2: ‘Intestinal Risk Factors, Diabetes, Dyslipidemia, and Heart Failure’, F-31432 Toulouse Cedex 4, France
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  • Marc-Emmanuel Dumas
    Section of Biomolecular Medicine, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdom

    Section of Genomic and Environmental Medicine, Respiratory Division, National Heart and Lung Institute, Imperial College London, Dovehouse St, London SW3 6KY, United Kingdom
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  • Richard H. Barton
    Section of Biomolecular Medicine, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdom
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  • Lesley Hoyles
    Department of Biosciences, Nottingham Trent University, Clifton Campus, Nottingham NG11 8NS, United Kingdom
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  • Massimo Federici
    Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
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  • José-Manuel Fernández-Real
    Corresponding author. Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University Hospital, Girona Biomedical Research Institute (IdIBGi), Carretera de França s/n, 17007 Girona, Spain. Fax: +34 97294027.
    Department of Endocrinology, Diabetes and Nutrition, Hospital of Girona “Dr Josep Trueta”, Departament de Ciències Mèdiques, University of Girona, Girona Biomedical Research Institute (IdibGi), Girona, Spain

    CIBERobn Pathophysiology of Obesity and Nutrition, Instituto de Salud Carlos III, Madrid, Spain
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Published:March 08, 2020DOI:


      Background & aims

      Atherosclerosis is characterized by an inflammatory disease linked to excessive lipid accumulation in the artery wall. The Notch signalling pathway has been shown to play a key regulatory role in the regulation of inflammation. Recently, in vitro and pre-clinical studies have shown that apolipoprotein A–I binding protein (AIBP) regulates cholesterol metabolism (SREBP) and NOTCH signalling (haematopoiesis) and may be protective against atherosclerosis, but the evidence in humans is scarce.


      We evaluated the APOA1bp–SREBF–NOTCH axis in association with atherosclerosis in two well-characterized cohorts of morbidly obese patients (n = 78) within the FLORINASH study, including liver transcriptomics, 1H NMR plasma metabolomics, high-resolution ultrasonography evaluating carotid intima-media thickness (cIMT), and haematological parameters.


      The liver expression levels of APOA1bp were associated with lower cIMT and leukocyte counts, a better plasma lipid profile and higher circulating levels of metabolites associated with lower risk of atherosclerosis (glycine, histidine and asparagine). Conversely, liver SREBF and NOTCH mRNAs were positively associated with atherosclerosis, liver steatosis, an unfavourable lipid profile, higher leukocytes and increased levels of metabolites linked to inflammation and CVD such as branched-chain amino acids and glycoproteins. APOA1bp and NOTCH signalling also had a strong association, as revealed by the negative correlations among APOA1bp expression levels and those of all NOTCH receptors and jagged ligands.


      We here provide the first evidence in human liver of the putative APOA1bpSREBF–NOTCH axis signalling pathway and its association with atherosclerosis and inflammation.


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