The effects of a 20-week exercise program on blood-circulating biomarkers related to brain health in overweight or obese children: The ActiveBrains project

María Rodriguez-Ayllon; Abel Plaza-Florido; Andrea Mendez-Gutierrez; Signe Altmäe; Patricio Solis-Urra; Concepción M Aguilera; Andrés Catena; Francisco B Ortega; Irene Esteban-Cornejo

doi:10.1016/j.jshs.2022.12.007

The effects of a 20-week exercise program on blood-circulating biomarkers related to brain health in overweight or obese children: The ActiveBrains project

J Sport Health Sci. 2023 Mar;12(2):175-185. doi: 10.1016/j.jshs.2022.12.007. Epub 2022 Dec 15.

Authors

María Rodriguez-Ayllon¹, Abel Plaza-Florido², Andrea Mendez-Gutierrez³, Signe Altmäe⁴, Patricio Solis-Urra⁵, Concepción M Aguilera³, Andrés Catena⁶, Francisco B Ortega⁷, Irene Esteban-Cornejo²

Affiliations

¹ PROFITH "PROmoting FITness and Health through physical activity" research group, Sport and Health University Research Institute (iMUDS), Department of Physical and Sports Education, Faculty of Sport Sciences, University of Granada, Granada 18071, Spain; Department of Epidemiology, Erasmus University Medical Center, Rotterdam 3015 GD, the Netherlands.
² PROFITH "PROmoting FITness and Health through physical activity" research group, Sport and Health University Research Institute (iMUDS), Department of Physical and Sports Education, Faculty of Sport Sciences, University of Granada, Granada 18071, Spain.
³ Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Granada 18071, Spain.
⁴ Department of Biochemistry and Molecular Biology, Faculty of Sciences, University of Granada, Granada 18071, Spain.
⁵ PROFITH "PROmoting FITness and Health through physical activity" research group, Sport and Health University Research Institute (iMUDS), Department of Physical and Sports Education, Faculty of Sport Sciences, University of Granada, Granada 18071, Spain; Nuclear Medicine Services, Virgen de Las Nieves University Hospital, Granada 18014, Spain; Faculty of Education and Social Sciences, Universidad Andres Bello, Viña del Mar 2531015, Chile.
⁶ Department of Experimental Psychology, School of Psychology, University of Granada, Granada 18011, Spain.
⁷ PROFITH "PROmoting FITness and Health through physical activity" research group, Sport and Health University Research Institute (iMUDS), Department of Physical and Sports Education, Faculty of Sport Sciences, University of Granada, Granada 18071, Spain; Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä 40014, Finland; Department of Bioscience and Nutrition, Karolinska Institutet, Huddinge, SE 141 57, Sweden. Electronic address: ortegaf@ugr.es.

Abstract

Background: Emerging research supports the idea that exercise positively affects neurodevelopment. However, the mechanisms linking exercise with brain health are largely unknown. We aimed to investigate the effect of exercise on (a) blood biomarkers selected based on previous evidence (brain-derived neurotrophic factor, β-hydroxybutyrate (BHB), cathepsin B (CTSB), kynurenine, fibroblast growth factor 21 (FGF21), soluble vascular cell adhesion molecule-1 (sVCAM-1)); and (b) a panel of 92 neurology-related proteins (discovery analysis). We also investigated whether changes in these biomarkers mediate the effects of exercise on brain health (hippocampal structure and function, cognitive performance, and mental health).

Methods: We randomized 81 overweight/obese children (10.1 ± 1.1 years, 41% girls) into 2 groups: either 20 weeks of aerobic plus resistance exercise or control. Candidate biomarkers were assessed using enzyme-linked immunosorbent assay (ELISA) for kynurenine, FGF21, and CTSB; colorimetry for β-hydroxybutyrate; and XMap for brain-derived neurotrophic factor and soluble vascular cell adhesion molecule-1. The 92 neurology-related proteins were analyzed by an antibody-based proteomic analysis.

Results: Our intervention had no significant effect on candidate biomarkers (all p > 0.05). In the discovery analysis, a reduction in circulating macrophage scavenger receptor type-I was observed (standardized differences between groups = -0.3, p = 0.001). This effect was validated using ELISA methods (standardized difference = -0.3, p = 0.01). None of the biomarkers mediated the effects of exercise on brain health.

Conclusions: Our study does not support a chronic effect of exercise on candidate biomarkers. We observed that while chronic exercise reduced the levels of macrophage scavenger receptor type-I, it did not mediate the effects of exercise on brain health. Future studies should explore the implications of this novel biomarker for overall health.

Keywords: Brain development; Childhood; MRI; Physical activity; Proteomic.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3-Hydroxybutyric Acid
Biomarkers
Brain
Brain-Derived Neurotrophic Factor
Child
Exercise Therapy
Female
Humans
Kynurenine
Male
Overweight* / therapy
Pediatric Obesity* / therapy
Proteomics
Vascular Cell Adhesion Molecule-1

Substances

Brain-Derived Neurotrophic Factor
Vascular Cell Adhesion Molecule-1
3-Hydroxybutyric Acid
Kynurenine
Biomarkers