Obesity is a protective evolutionary mechanism that helped humankind survive famine and, as such, is as old as humanity. This once adaptive mechanism has become counterproductive in modern society, due to unprecedented lifestyle changes that have resulted in an obesity epidemic on a global scale, with 1.5 billion adults and 200 million children and adolescents being overweight or obese [1–4].
Some of the obesogenic factors in the environment include the constant availability and affordability of food in general, and especially processed foods and sugary drinks [5–7]. In addition, the reduction in physical activity at home and in school , the reliance on the use of technology, and shorter duration of sleep  are some of the precursors involved in the genesis of childhood obesity. These elements interact with each other and with genetic and epigenetic factors to mediate the body’s response to excess weight, and this is an area of intensive research. However, the mechanisms that lead to the initiation of obesity are not yet identified, and understanding the mechanisms that start and propagate obesity will help define interventions for its treatment and prevention.
The significance of childhood obesity lies in its association with other comorbidities in children including glucose intolerance, type 2 diabetes, dyslipidemia, hypertension, obstructive sleep apnea, gastroesophageal reflux, and joint problems . In addition, many obese children are likely to become obese adults, with increased risk of adverse health outcomes including cardiovascular disease and diabetes [10, 11].
Pediatric weight management programs focus on life style interventions to manage obesity, and one pillar of these programs is exercise . An important aspect of designing exercise regimens involves the determination of fitness levels to aid with the provision of a targeted exercise plan. Fitness testing requires the existence of a significant infrastructure of equipment and trained personnel, adding to the complexity and cost of care provided. To date, there has been no fitness biomarkers identified that allows us to allocate children to specific exercise programs without the need for costly exercise testing.
On a mechanistic level, obesity is associated with a chronic low-grade inflammatory state , characterized by activation of the innate immune system and infiltration of immune cells into metabolic organs including adipose tissue, skeletal muscle and liver [14, 15].
The signals that attract immune cells into these organs include a set of cytokines, called chemokines, that have the ability to regulate leukocyte traffic into tissues .
One such chemokine is Chemokine (C-C motif) Ligand 2 (CCL2), also known as Monocyte Chemoattractant Protein-1 (MCP-1). The adipocyte is a major source of CCL2 in obesity, the production of which is triggered when cells are exposed to inflammatory cytokines and fatty acids , and recently, microRNAs 126 and 193b have also been implicated in the regulation of CCL2 secretion in obese adipose tissue . Other cells are capable of secreting CCL2 in obesity including hepatocytes , skeletal muscle cells , monocytes, vascular smooth muscle and endothelial cells .
The role of CCL2 in childhood obesity is not well studied. Circulating CCL2 levels are increased in obese adults and children [21, 22], and correlate positively with BMI and other inflammatory markers like C-Reactive Protein and Interleukin-6 and negatively with High Density lipoprotein (HDL) . CCL2 administration causes insulin resistance in mice , although there is conflicting evidence to its correlation with insulin resistance in adult humans [23, 25, 26].
In addition, CCL2 has also been implicated in monocyte infiltration into atherosclerotic plaques and exacerbation of atherosclerosis . Weight loss and exercise lead to a reduction in CCL2 levels, and improved insulin sensitivity [22, 28].
While CCL2 has been implicated in inflammation and insulin resistance, its correlation with fitness has not been studied previously. As CCL2 levels are elevated in obesity and is associated with inflammation and insulin resistance, and as exercise lowers CCL2 levels, the aim of this study was to test the hypothesis that CCL2 levels are higher in obese children when compared to lean controls, and that CCL2 levels are higher in children with low fitness levels when compared to fit children reflecting a more robust inflammatory response. We predicted that this molecule could serve a dual role as a biomarker of fitness and inflammation in children.