The association between body mass index and metabolite response to a liquid mixed meal challenge: a Mendelian randomization study.
causal inference
instrumental variable analysis
lipidomics
metabolomics
obesity
Journal
The American journal of clinical nutrition
ISSN: 1938-3207
Titre abrégé: Am J Clin Nutr
Pays: United States
ID NLM: 0376027
Informations de publication
Date de publication:
15 Mar 2024
15 Mar 2024
Historique:
received:
09
10
2023
revised:
30
01
2024
accepted:
12
03
2024
medline:
18
3
2024
pubmed:
18
3
2024
entrez:
17
3
2024
Statut:
aheadofprint
Résumé
Metabolite abundance is a dynamic trait that varies in response to environmental stimuli and phenotypic traits, such as food consumption and body mass index (BMI). Here we use the Netherlands Epidemiology of Obesity (NEO) study to identify observational and causal associations between BMI and metabolite response to a liquid meal. A liquid meal challenge was performed and Nightingale Health metabolite profiles were collected in 5744 NEO participants. Observational and one-sample MR analysis were conducted to estimate the effect of BMI on metabolites (n = 229) in the fasting, postprandial and response (or change in abundance) states. We observed 473 associations with BMI (175 fasting, 188 postprandial, 110 response) in observational analyses. In MR analyses, we observed 20 metabolite traits (5 fasting, 12 postprandial, 3 response) to be associated with BMI. MR associations included the glucogenic amino acid alanine which was inversely associated with BMI in the response state (beta = -0.081, se = 0.023, P = 5.91x10 Overall, MR estimates were strongly correlated with observational effect estimates suggesting that the broad associations seen between BMI and metabolite variation has a causal underpinning. Specific effects in previously unassessed postprandial and response states were detected and these may likely mark novel life course risk exposures driven by regular nutrition.
Sections du résumé
BACKGROUND
BACKGROUND
Metabolite abundance is a dynamic trait that varies in response to environmental stimuli and phenotypic traits, such as food consumption and body mass index (BMI).
OBJECTIVES
OBJECTIVE
Here we use the Netherlands Epidemiology of Obesity (NEO) study to identify observational and causal associations between BMI and metabolite response to a liquid meal.
METHODS
METHODS
A liquid meal challenge was performed and Nightingale Health metabolite profiles were collected in 5744 NEO participants. Observational and one-sample MR analysis were conducted to estimate the effect of BMI on metabolites (n = 229) in the fasting, postprandial and response (or change in abundance) states.
RESULTS
RESULTS
We observed 473 associations with BMI (175 fasting, 188 postprandial, 110 response) in observational analyses. In MR analyses, we observed 20 metabolite traits (5 fasting, 12 postprandial, 3 response) to be associated with BMI. MR associations included the glucogenic amino acid alanine which was inversely associated with BMI in the response state (beta = -0.081, se = 0.023, P = 5.91x10
CONCLUSIONS
CONCLUSIONS
Overall, MR estimates were strongly correlated with observational effect estimates suggesting that the broad associations seen between BMI and metabolite variation has a causal underpinning. Specific effects in previously unassessed postprandial and response states were detected and these may likely mark novel life course risk exposures driven by regular nutrition.
Identifiants
pubmed: 38494119
pii: S0002-9165(24)00344-7
doi: 10.1016/j.ajcnut.2024.03.009
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024. Published by Elsevier Inc.