Apt interpretation of comprehensive lipoprotein data in large-scale epidemiology: disclosure of fundamental structural and metabolic relationships.
NMR spectroscopy
apolipoproteins
lipoprotein composition
lipoprotein lipids
lipoprotein subclasses
metabolomics
Journal
International journal of epidemiology
ISSN: 1464-3685
Titre abrégé: Int J Epidemiol
Pays: England
ID NLM: 7802871
Informations de publication
Date de publication:
13 06 2022
13 06 2022
Historique:
received:
15
01
2021
accepted:
09
07
2021
pubmed:
19
8
2021
medline:
15
6
2022
entrez:
18
8
2021
Statut:
ppublish
Résumé
Quantitative lipoprotein analytics using nuclear magnetic resonance (NMR) spectroscopy is currently commonplace in large-scale studies. One methodology has become widespread and is currently being utilized also in large biobanks. It allows the comprehensive characterization of 14 lipoprotein subclasses, clinical lipids, apolipoprotein A-I and B. The details of these data are conceptualized here in relation to lipoprotein metabolism with particular attention on the fundamental characteristics of subclass particle numbers, lipid concentrations and compositional measures. The NMR methodology was applied to fasting serum samples from Northern Finland Birth Cohorts 1966 and 1986 with 5651 and 5605 participants, respectively. All results were highly consistent between the cohorts. Circulating lipid concentrations in a particular lipoprotein subclass arise predominantly as the result of the circulating number of those subclass particles. The spherical lipoprotein particle shape, with a radially oriented surface monolayer, imposes size-dependent biophysical constraints for the lipid composition of individual subclass particles and inherently restricts the accommodation of metabolic changes via compositional modifications. The new finding that the relationship between lipoprotein subclass particle concentrations and the particle size is log-linear reveals that circulating lipoprotein particles are also under rather strict metabolic constraints for both their absolute and relative concentrations. The fundamental structural and metabolic relationships between lipoprotein subclasses elucidated in this study empower detailed interpretation of lipoprotein metabolism. Understanding the intricate details of these extensive data is important for the precise interpretation of novel therapeutic opportunities and for fully utilizing the potential of forthcoming analyses of genetic and metabolic data in large biobanks.
Sections du résumé
BACKGROUND
Quantitative lipoprotein analytics using nuclear magnetic resonance (NMR) spectroscopy is currently commonplace in large-scale studies. One methodology has become widespread and is currently being utilized also in large biobanks. It allows the comprehensive characterization of 14 lipoprotein subclasses, clinical lipids, apolipoprotein A-I and B. The details of these data are conceptualized here in relation to lipoprotein metabolism with particular attention on the fundamental characteristics of subclass particle numbers, lipid concentrations and compositional measures.
METHODS AND RESULTS
The NMR methodology was applied to fasting serum samples from Northern Finland Birth Cohorts 1966 and 1986 with 5651 and 5605 participants, respectively. All results were highly consistent between the cohorts. Circulating lipid concentrations in a particular lipoprotein subclass arise predominantly as the result of the circulating number of those subclass particles. The spherical lipoprotein particle shape, with a radially oriented surface monolayer, imposes size-dependent biophysical constraints for the lipid composition of individual subclass particles and inherently restricts the accommodation of metabolic changes via compositional modifications. The new finding that the relationship between lipoprotein subclass particle concentrations and the particle size is log-linear reveals that circulating lipoprotein particles are also under rather strict metabolic constraints for both their absolute and relative concentrations.
CONCLUSIONS
The fundamental structural and metabolic relationships between lipoprotein subclasses elucidated in this study empower detailed interpretation of lipoprotein metabolism. Understanding the intricate details of these extensive data is important for the precise interpretation of novel therapeutic opportunities and for fully utilizing the potential of forthcoming analyses of genetic and metabolic data in large biobanks.
Identifiants
pubmed: 34405869
pii: 6354147
doi: 10.1093/ije/dyab156
pmc: PMC9189959
doi:
Substances chimiques
Lipoproteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
996-1011Subventions
Organisme : Medical Research Council
ID : MR/S019669/1
Pays : United Kingdom
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of the International Epidemiological Association.
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