Review
Obesity and inflammation in children

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Summary

Systemic inflammation is present in children and adults with obesity. Inflammation associated with obesity appears to be central to the development of insulin resistance and atherosclerosis and may be important in the pathogenesis of other comorbid conditions. Although generally considered an inert energy storage tissue, white adipose tissue is a metabolically active organ. It produces a number of inflammatory cytokines and acute-phase reactants. Inflammation associated with obesity declines after weight loss and with exercise. It may also be possible to modify obesity-associated inflammation with medications, reducing comorbidities without weight loss. The study of inflammation in the context of excessive adipose tissue is central to understanding obesity and modifying its impact on patients.

Introduction

Obesity, a condition resulting from an excess of adipose tissue, has an adverse impact on health. The disability and shortened life span associated with obesity are consequences of comorbid conditions, including insulin resistance, type 2 diabetes, atherosclerotic heart disease, non-alcoholic fatty liver disease, hypertension and hyperlipidaemia. Although the pathogenesis of these conditions is not clearly defined, it is generally accepted that it is related, in part, to the metabolic activity of adipose tissue acting via elevated levels of inflammatory factors, similar to those seen in infection and autoimmune disease.

Inflammation is a primary immune mechanism, sometimes termed ‘innate immunity’. In common acute conditions, e.g. infection and localised trauma, the inflammatory response is the first line of defence. Significant deficiencies in the inflammatory cascade, e.g. the absence of primary inflammatory mediators such as interleukin (IL)-6 or tumour necrosis factor-α (TNF-α), are associated with increased morbidity and mortality.1, 2, 3 However, chronic low-grade levels of inflammation also occur. In obese individuals,4, 5 these are strongly associated with the development of insulin resistance, atherosclerosis and other obesity-related conditions (Table 1).

This review will discuss the relationship between obesity and inflammation in children. It will include a discussion of adipose tissue as a metabolically active organ, the association of inflammation with comorbid conditions of obesity and evidence that modulating inflammation alters obesity and/or its comorbidities.

Section snippets

Classical inflammation and innate immunity

The classic inflammatory response is predominantly a function of the macrophage.6, 7 Inflammation is triggered in macrophages through the Toll-like receptor family. Ten members of this family have been identified, each with specific ligand recognition for various bacterial and fungal proteins. Toll-like receptor 4 (TLR4), which recognises the ligand lipopolysaccharide (LPS), is the best characterised of this family. When LPS is recognised by the TLR4 receptor, it initiates a signalling cascade

Obesity-related inflammation

Obesity is associated with systemic inflammation,5 as evidenced by studies documenting the association of body mass index (BMI) and visceral obesity with circulating levels of cytokines and acute-phase reactants.4, 10, 11 Although the liver participates in the systemic inflammation of obesity, in contrast to the classic inflammatory response, the dominant controlling organ is the adipose tissue.

Early studies showed that adipose tissue of obese mice contained quantitatively more TNF-α mRNA than

Obesity and Inflammation in Children

Obese children of all ages have evidence of a low-grade chronic inflammatory state. In this sense, even the very youngest obese children do not differ from obese adults. In some cases, the degree of inflammation, as measured by circulating acute-phase reactants and cytokines, is correlated with the presence of several of the comorbid conditions of obesity, including insulin resistance, dyslipidaemia, non-alcoholic fatty liver disease (NAFLD), atherosclerosis and hypercoagulation. Direct

Treatment of obesity-related inflammation

The increasing evidence for systemic inflammation in the pathogenesis of comorbid conditions of obesity suggests that therapeutic modification of inflammation might influence their development. Few such studies have been performed in children but information is available from studies in adults.

Summary

Inflammation in obesity is involved in the pathogenesis of a number of serious complications and this effect extends across the age spectrum. The outcome of >30% of children living the majority of their developmental years in a chronic inflammatory state is unknown. Weight loss and lifestyle changes can modify obesity-induced inflammation and some medications can modify obesity-induced inflammation in the absence of weight loss. The study of inflammation in the context of excessive adipose

Practice points

  • Obesity in childhood is associated with systemic inflammation, correlated with BMI.

  • Inflammation is associated with many of the complications of obesity and is pathogenic in insulin resistance, atherosclerosis and, possibly, in NAFLD.

  • Weight loss and/or exercise may reduce systemic inflammation.

Research directions

  • The mechanism by which increasing adiposity triggers inflammation.

  • The prevalence of inflammation in very young obese patients and the impact of life-long inflammation on growth and development.

  • The impact of maternal inflammation in the children of obese mothers.

  • The role of inflammation in the pathogenesis of other comorbid conditions of obesity, e.g. cancer risk, polycystic ovary syndrome and depression.

Acknowledgements

Dr. Sinaiko is supported by Grants No. HL52851 and M01RR00400 from the National Institutes of Health.

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