Transcriptional, epigenetic and metabolic signatures in cardiometabolic syndrome defined by extreme phenotypes.
Bariatric surgery
Cardiometabolic syndrome
Classification
Epigenetics
Innate immune cells
Lipids
Lipodystrophy
Metabolites
Multi-omics
Obesity
Journal
Clinical epigenetics
ISSN: 1868-7083
Titre abrégé: Clin Epigenetics
Pays: Germany
ID NLM: 101516977
Informations de publication
Date de publication:
12 03 2022
12 03 2022
Historique:
received:
16
11
2021
accepted:
25
02
2022
entrez:
13
3
2022
pubmed:
14
3
2022
medline:
7
5
2022
Statut:
epublish
Résumé
This work is aimed at improving the understanding of cardiometabolic syndrome pathophysiology and its relationship with thrombosis by generating a multi-omic disease signature. We combined classic plasma biochemistry and plasma biomarkers with the transcriptional and epigenetic characterisation of cell types involved in thrombosis, obtained from two extreme phenotype groups (morbidly obese and lipodystrophy) and lean individuals to identify the molecular mechanisms at play, highlighting patterns of abnormal activation in innate immune phagocytic cells. Our analyses showed that extreme phenotype groups could be distinguished from lean individuals, and from each other, across all data layers. The characterisation of the same obese group, 6 months after bariatric surgery, revealed the loss of the abnormal activation of innate immune cells previously observed. However, rather than reverting to the gene expression landscape of lean individuals, this occurred via the establishment of novel gene expression landscapes. NETosis and its control mechanisms emerge amongst the pathways that show an improvement after surgical intervention. We showed that the morbidly obese and lipodystrophy groups, despite some differences, shared a common cardiometabolic syndrome signature. We also showed that this could be used to discriminate, amongst the normal population, those individuals with a higher likelihood of presenting with the disease, even when not displaying the classic features.
Sections du résumé
BACKGROUND
This work is aimed at improving the understanding of cardiometabolic syndrome pathophysiology and its relationship with thrombosis by generating a multi-omic disease signature.
METHODS/RESULTS
We combined classic plasma biochemistry and plasma biomarkers with the transcriptional and epigenetic characterisation of cell types involved in thrombosis, obtained from two extreme phenotype groups (morbidly obese and lipodystrophy) and lean individuals to identify the molecular mechanisms at play, highlighting patterns of abnormal activation in innate immune phagocytic cells. Our analyses showed that extreme phenotype groups could be distinguished from lean individuals, and from each other, across all data layers. The characterisation of the same obese group, 6 months after bariatric surgery, revealed the loss of the abnormal activation of innate immune cells previously observed. However, rather than reverting to the gene expression landscape of lean individuals, this occurred via the establishment of novel gene expression landscapes. NETosis and its control mechanisms emerge amongst the pathways that show an improvement after surgical intervention.
CONCLUSIONS
We showed that the morbidly obese and lipodystrophy groups, despite some differences, shared a common cardiometabolic syndrome signature. We also showed that this could be used to discriminate, amongst the normal population, those individuals with a higher likelihood of presenting with the disease, even when not displaying the classic features.
Identifiants
pubmed: 35279219
doi: 10.1186/s13148-022-01257-z
pii: 10.1186/s13148-022-01257-z
pmc: PMC8917653
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
39Subventions
Organisme : Medical Research Council
ID : MC_UU_00006/1
Pays : United Kingdom
Organisme : MRC Clinical Research Training Fellowships
ID : MR/R002363/1
Organisme : Medical Research Council
ID : MR/R002363/1
Pays : United Kingdom
Organisme : MRC Metabolic Disease Unit
ID : MRC_MC_UU_12012.1
Organisme : Medical Research Council
ID : MC_UU_00002/13
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/18/53/33863
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT 107064
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
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