The APOA1bp-SREBF-NOTCH axis is associated with reduced atherosclerosis risk in morbidly obese patients.
Adult
Asparagine
/ metabolism
Atherosclerosis
/ etiology
Biopsy
Carotid Intima-Media Thickness
Cross-Sectional Studies
Female
Glycine
/ metabolism
Histidine
/ metabolism
Humans
Inflammation
Liver
/ metabolism
Male
Metabolome
Middle Aged
Obesity, Morbid
/ complications
RNA, Messenger
/ metabolism
Racemases and Epimerases
/ metabolism
Receptors, Notch
/ metabolism
Signal Transduction
/ genetics
Sterol Regulatory Element Binding Proteins
/ metabolism
Transcriptome
Young Adult
Apolipoprotein A1 binding protein
Atherosclerosis
Haematopoiesis
Inflammation
NOTCH
SREBF
Journal
Clinical nutrition (Edinburgh, Scotland)
ISSN: 1532-1983
Titre abrégé: Clin Nutr
Pays: England
ID NLM: 8309603
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
03
12
2019
revised:
23
01
2020
accepted:
24
02
2020
pubmed:
23
3
2020
medline:
20
8
2021
entrez:
23
3
2020
Statut:
ppublish
Résumé
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, 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 APOA1bp-SREBF-NOTCH axis signalling pathway and its association with atherosclerosis and inflammation.
Sections du résumé
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.
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,
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.
Identifiants
pubmed: 32199697
pii: S0261-5614(20)30098-4
doi: 10.1016/j.clnu.2020.02.034
pii:
doi:
Substances chimiques
RNA, Messenger
0
Receptors, Notch
0
Sterol Regulatory Element Binding Proteins
0
Histidine
4QD397987E
Asparagine
7006-34-0
NAXE protein, human
EC 5.1.-
Racemases and Epimerases
EC 5.1.-
Glycine
TE7660XO1C
Types de publication
Evaluation Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3408-3418Subventions
Organisme : Medical Research Council
ID : MR/L01632X/1
Pays : United Kingdom
Informations de copyright
Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.