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Eight-year diet and physical activity intervention affects serum metabolites during childhood and adolescence: A nonrandomized controlled trial.

ABSTRACT: Long-term lifestyle interventions in childhood and adolescence can significantly improve cardiometabolic health, but the underlying molecular mechanisms remain poorly understood. To address this knowledge gap, we conducted an 8-year diet and physical activity intervention in a general population of children. The research revealed that the intervention influenced 80 serum metabolites over two years, with 17 metabolites continuing to be affected after eight years. The intervention primarily impacted fatty amides, including palmitic amide, linoleamide, oleamide, and others, as well as unsaturated fatty acids, acylcarnitines, phospholipids, sterols, gut microbiota-derived metabolites, amino acids, and purine metabolites. Particularly noteworthy were the pronounced changes in serum fatty amides. These serum metabolite alterations could represent molecular mechanisms responsible for the observed benefits of long-term lifestyle interventions on cardiometabolic and overall health since childhood. Understanding these metabolic changes may provide valuable insights into the prevention of cardiometabolic and other non-communicable diseases since childhood.

SUBMITTER: Zarei I

PROVIDER: S-EPMC11269805 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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Eight-year diet and physical activity intervention affects serum metabolites during childhood and adolescence: A nonrandomized controlled trial.

Zarei Iman I Eloranta Aino-Maija AM Klåvus Anton A Väistö Juuso J Lehtonen Marko M Mikkonen Santtu S Koistinen Ville M VM Sallinen Taisa T Haapala Eero A EA Lintu Niina N Soininen Sonja S Haikonen Retu R Atalay Mustafa M Schwab Ursula U Auriola Seppo S Kolehmainen Marjukka M Hanhineva Kati K Lakka Timo A TA

iScience 20240617 7

Long-term lifestyle interventions in childhood and adolescence can significantly improve cardiometabolic health, but the underlying molecular mechanisms remain poorly understood. To address this knowledge gap, we conducted an 8-year diet and physical activity intervention in a general population of children. The research revealed that the intervention influenced 80 serum metabolites over two years, with 17 metabolites continuing to be affected after eight years. The intervention primarily impact ...[more]

PMID: 39055945

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Project description:BackgroundChildhood adiposity is inversely associated with young adult percent dense breast volume (%DBV) and absolute dense breast volume (ADBV), which could contribute to its protective effect for breast cancer later in life. The objective of this study was to identify metabolites in childhood serum that may mediate the inverse association between childhood adiposity and young adult breast density.MethodsLongitudinal data from 182 female participants in the Dietary Intervention Study in Children (DISC) and the DISC 2006 (DISC06) Follow-Up Study were analyzed. Childhood adiposity was assessed by anthropometry at the DISC visit with serum available that occurred closest to menarche and expressed as a body mass index (BMI) z-score. Serum metabolites were measured by untargeted metabolomics using ultra-high-performance liquid chromatography-tandem mass spectrometry. %DBV and ADBV were measured by magnetic resonance imaging at the DISC06 visit when participants were 25-29 years old. Robust mixed effects linear regression was used to identify serum metabolites associated with childhood BMI z-scores and breast density, and the R package mediation was used to quantify mediation.ResultsOf the 115 metabolites associated with BMI z-scores (FDR < 0.20), 4 were significantly associated with %DBV and 6 with ADBV before, though not after, adjustment for multiple comparisons. Mediation analysis identified 2 unnamed metabolites, X-16576 and X-24588, as potential mediators of the inverse association between childhood adiposity and dense breast volume. X-16576 mediated 14% (95% confidence interval (CI) = 0.002, 0.46; P = 0.04) of the association of childhood adiposity with %DBV and 11% (95% CI = 0.01, 0.26; P = 0.02) of its association with ADBV. X-24588 also mediated 7% (95% CI = 0.001, 0.18; P = 0.05) of the association of childhood adiposity with ADBV. None of the other metabolites examined contributed to mediation of the childhood adiposity-%DBV association, though there was some support for contributions of lysine, valine and 7-methylguanine to mediation of the inverse association of childhood adiposity with ADBV.ConclusionsAdditional large longitudinal studies are needed to identify metabolites and other biomarkers that mediate the inverse association of childhood adiposity with breast density and possibly breast cancer risk.

Dataset Information

Eight-year diet and physical activity intervention affects serum metabolites during childhood and adolescence: A nonrandomized controlled trial.

Publications

Eight-year diet and physical activity intervention affects serum metabolites during childhood and adolescence: A nonrandomized controlled trial.

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