The APOA1BP-SREBF-NOTCH axis is associated with reduced atherosclerosis risk in morbidly obese patients

Mayneris-Perxachs, J, Puig, J, Burcelin, R, Dumas, M-E, Barton, RH, Hoyles, L ORCID: https://orcid.org/0000-0002-6418-342X, Federici, M and Fernández-Real, J-M, 2020. The APOA1BP-SREBF-NOTCH axis is associated with reduced atherosclerosis risk in morbidly obese patients. Clinical Nutrition. ISSN 0261-5614

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Abstract

Background and 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.

Methods: 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.

Results: 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.

Conclusions: We here provide the first evidence in human liver of the putative APOA1BP-SREBF-NOTCH axis signalling pathway and its association with atherosclerosis and inflammation.

Item Type:	Journal article
Publication Title:	Clinical Nutrition
Creators:	Mayneris-Perxachs, J., Puig, J., Burcelin, R., Dumas, M.-E., Barton, R.H., Hoyles, L., Federici, M. and Fernández-Real, J.-M.
Publisher:	Elsevier
Date:	8 March 2020
ISSN:	0261-5614
Identifiers:	Number Type 10.1016/j.clnu.2020.02.034 DOI S0261561420300984 Publisher Item Identifier 1302429 Other
Divisions:	Schools > School of Science and Technology
Record created by:	Jonathan Gallacher
Date Added:	11 Mar 2020 11:24
Last Modified:	31 May 2021 15:06
URI:	https://irep.ntu.ac.uk/id/eprint/39384

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