Effects of Different Doses of Exercise on Inflammation Markers Among Adolescents With Overweight/Obesity: HEPAFIT Study

Robinson Ramírez-Vélez, Antonio García-Hermoso, María Correa-Rodríguez, Joaquín Fernández-Irigoyen, Sara Palomino-Echeverría, Enrique Santamaría, Jorge Enrique Correa-Bautista, Katherine González-Ruíz, Mikel Izquierdo, Robinson Ramírez-Vélez, Antonio García-Hermoso, María Correa-Rodríguez, Joaquín Fernández-Irigoyen, Sara Palomino-Echeverría, Enrique Santamaría, Jorge Enrique Correa-Bautista, Katherine González-Ruíz, Mikel Izquierdo

Abstract

Propose: Obesity-related metabolic risk factors in adolescents who are overweight/obese may be associated with systemic low-grade inflammation; therefore, we investigated whether 6 months of exercise training altered markers of inflammation.

Methods: Secondary analyses of a randomized controlled exercise-based intervention trial (September 2017-December 2018). Adolescents aged 11 to 17 years (Tanner stage II-V), 70% girls, with a body mass index z-score at or above the 85th percentile, and/or with excess of adiposity (body fat ≥ 30%). The participants were randomly assigned to the following 4 groups for 6 months: (1) standard physical education lessons, as a control (CTRL); (2) high-intensity physical education class (HIPE); (3) low-to-moderate intensity physical education class (LIPE); (4) a combined group (PLUS). Inflammatory markers and immune molecules including chemokines, cytokines, and growth factors (n = 65 biomarkers) were determined by cytokine antibody array.

Results: Of the 120 randomly assigned participants, 95 were included in the analysis. Considering these 22 proteins, the LIPE group shows statistical significance in 9 proteins with log-fold change (logFC) and P < 0.05 (in BLC, eotaxin, fibroblast growth factor-6 [FGF-6], GCP-2, I-309, IGFBP-4, MCP-4, NAP-2, and PARC), followed by the PLUS group in 9 proteins (BLC, pro-epidermal growth factor, eotaxin, FGF-6, MCP-4, NAP-2, osteopontin, PARC, and RANTES), the HIPE group in 7 proteins (FGF-4, FGF-7, GCP-2, IGF-1, IGFBP-1, IGFBP-4, and MIP-1 delta), and the CTRL group in 6 proteins (FGF-4, IP-10, Leptin, MCP-1, MIG, and MIP-1 delta). However, subanalysis performed to detect differentially expressed proteins at baseline and after intervention, with significance at an adjusted P value ≤ 0.05 and absolute log fold-change (logFC) ≥ 1.0, showed 3 downregulated proteins in the LIPE group (BLC(logFC) = 1.27, eotaxin(logFC) = 1.18, and MCP-4(logFC) = 1.14), and 4 proteins in the HIPE group (BLC(logFC) = 1.45, FGF-6(logFC) = 1.20, MCP-4(logFC) = 1.50, and PARC(logFC) = 1.33), supporting that the changes we observed in the exercise groups were not time-related changes but occurred in response to exercise.

Conclusions: Implementing a 6-month physical exercise program in overweight/obese adolescents, based on LIPE and PLUS groups, significantly change several circulating inflammatory levels. Interventions involving supervised physical exercise may reduce the associated effects of systemic low-grade inflammation, thus preventing the development of obesity-related metabolic diseases in adolescents with overweight/obesity.

Trial registration: ClinicalTrials.gov NCT02753231.

Keywords: exercise; inflammation; obesity; youth.

© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Figures

Figure 1.
Figure 1.
Participant flow diagram.
Figure 2.
Figure 2.
Change in inflammatory markers and immune molecules including chemokines, cytokines, and growth factors in response to exercise (log fold-change) from the baseline in 22/65 proteins. The letters (a-g) represent comparison of least squares means of the outcome. (a) CTRL vs LIPE P < 0.05; (b) CTRL vs LIPE P < 0.01; (c) CTRL vs PLUS P < 0.05; (d) CTRL vs PLUS P < 0.01; (e) CTRL vs HIPE P < 0.05; (f) CTRL vs HIPE P < 0.01; (g) HIPE vs PLUS P < 0.05.
Figure 3.
Figure 3.
Interactome network for deregulated cytokines. (A) Network analysis was performed submitting the corresponding protein identifications to the STRING (Search Tool for the Retrieval of Interacting Genes) software (v.11) (http://stringdb.org/). Only interactions tagged with > 0.4 confidence in the STRING database were considered. (B) Functional protein interactome networks were constructed, revealing commonalities and differences in the known functional relationships established between deregulated cytokines and growth factors observed at follow-up. The proteins are represented with nodes and edges (physical or functional interactions), supported by at least 2 reference from the published literature or from canonical information stored in the STRING database.

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