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May 15, 2023

Pediatric Obesity Research Update | Use of Physical Activity and Exercise to Reduce Inflammation in Children and Adolescents with Obesity

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Each month, the OMA Pediatric Committee reviews a pediatric-focused obesity research update to help keep you up to date about the latest findings. This month’s update addresses psychiatric disorders and obesity.

Use of Physical Activity and Exercise to Reduce Inflammation in Children and Adolescents with Obesity

Article Summary

This article is a narrative review discussing how excess adipose tissue promotes chronic inflammation with resultant poor health effects and the role of exercise in reducing those effects in children and adolescents. This article provides a nice summary and critical analysis of the current knowledge of how exercise can reduce obesity-related inflammation. Read the full article.

Article Review

As the prevalence of childhood obesity continues to increase worldwide, it is a leading public health problem, given its known risk of developing serious chronic diseases. At the core of the prevention and treatment of pediatric obesity is lifestyle modifications. A lack of physical activity and increased sedentary time is strongly associated with obesity and the accumulation of excess adipose tissue. Recent evidence suggests excess adipose tissue leads to low-grade systemic inflammation through immune cell infiltration and increased adipokine release. Exercise is a non-pharmacological intervention that can mitigate the inflammatory process and aid in reducing known obesity-related comorbidities. The anti-inflammatory effect of regular exercise is likely mediated by a reduction in visceral fat mass, thus resulting in a decreased release of adipokines from adipose tissue. A summary of the researched mechanisms relating to inflammation, adipose tissue, and exercise follows:

  • Adipose tissue and associated inflammation:
    In addition to being an effective endocrine organ, adipose tissue (AT) has been defined by researchers as a real immune organ involved in homeostasis with its extracellular matrix containing leukocytes (macrophages, mast cells, neutrophils, monocytes, natural killer cells, T and B lymphocytes). In a positive energy balance state, AT undergoes changes that lead to a massive release of pro-inflammatory cytokines and acute-phase proteins producing chronic low-grade inflammation.
    • Macrophages present in AT increase in quantity and undergo a shift from the M2 subtype (anti-inflammatory) to the M1 subtype (pro-inflammatory). Anti-inflammatory M2’s secrete IL-10, which helps maintain insulin sensitivity and glucose tolerance. The shift toward M1 leads to the secretion of TNF and IL-6, whose elevated concentrations positively correlate with the development of insulin resistance and the onset of type 2 DM.
    • Mast cells and neutrophils are increased in excess AT and release TNF-alpha, IL-1b, IL-6, IL-4, and elastase, all of which promote the pro-inflammatory state, increasing insulin resistance.
    • B lymphocytes are activated and produce antibodies that, in turn, activate macrophages, promoting inflammation.
    • T lymphocyte (CD4) activation leads to insulin resistance. Th17 cells secrete pro-inflammatory IL-17 leading to a cascade of release of other molecules activating the immune system.
    • Treg lymphocytes secreting IL-10 are decreased in excess AT. IL-10 maintains macrophages in the M2 state, promoting insulin sensitivity.
    • Adiponectin is reduced in excess AT, which reduces its anti-inflammatory cytokines leading to insulin resistance.
    • Leptin receptors on immune cells are activated, leading to insulin resistance.
    • Resistin and Chemerin adipokines promote the release of pro-inflammatory cytokines and the maintenance of low-grade inflammation respectively.
  • Anti-inflammatory effect of exercise in children and adolescents with obesity:
    Excessive AT accumulation can be prevented with physical activity, and with its anti-inflammatory effects, physical activity can be protective against chronic disease. Higher levels of physical activity and lower levels of sedentary time in children have been associated with lower levels of circulating inflammatory biomarkers.
    • Inflammatory biomarkers inversely associated with physical activity include CRP, IL-6, and TNF-alpha.
    • Skeletal muscle produces myokines (the most studied is IL-6) in response to contraction that have positive metabolic effects on the liver, pancreas, adipose tissue, and cardiovascular system.
    • Skeletal muscle-derived IL-6 triggers an anti-inflammatory cascade releasing IL-10 and inhibiting the release of pro-inflammatory cytokines TNF-alpha and IL-1B.
    • Cortisol and adrenaline production is increased with exercise, both of which have potent anti-inflammatory effects through muscle contraction.
    • Irisin myokine secretion induces the transformation of white adipocytes to “brite” (brown-white) cells raising thermogenesis and energy expenditure.
    • IL-15 in skeletal muscle reduces abdominal fat.
    • TLRs (transmembrane proteins on that help recognize microbial pathogens and danger signals of damage) on immune cells are decreased. TLRs are augmented and activated in physical inactivity, causing systemic inflammation associated with chronic non-communicable diseases.
  • Conclusion:
    Muscular contraction occurring during physical activity produces myokines which identifies skeletal muscle as an endocine organ capable of producing beneficial metabolic and immunologic effects, reducing systemic inflammation. This reduction in inflammation is an important non-pharmacological treatment in overweight and obesity to help attenuate its related comorbidities.

Additional Resources

Find more resources curated by OMA’s Pediatric Committee on our Pediatric Resources page. There you’ll find additional article reviews on various topics related to obesity as well as public resources for clinicians and families.

Calcaterra V, Vandoni M, Rossi V, Berardo C, Grazi R, Cordaro E, Tranfaglia V, Carnevale Pellino V, Cereda C, Zuccotti G. Use of Physical Activity and Exercise to Reduce Inflammation in Children and Adolescents with Obesity. Int J Environ Res Public Health. 2022 Jun 5;19(11):6908. doi: 10.3390/ijerph19116908. PMID: 35682490; PMCID: PMC9180584.