The prevention of obesity and health concerns related to excessive body fat are major challenges worldwide, especially considering the effect of childhood and adolescent obesity on our productive population in the near future. Therefore, using a holistic approach and multidisciplinary therapies, addressing related risk factors including a reduction in the prevalence of metabolic syndrome (MS), nonalcoholic fatty liver disease (NAFLD), asthma, and dyslipidemia whilst promoting improved quality of life and health, is valid.
Corroborating, data using the IDF criteria showed that 70% of obese women had diagnosis to MS. Moreover, an alarming prevalence of MS in childhood was found, suggesting therefore a focus on primary prevention and the promotion of healthy lifestyles. In addition, it was suggested that diet, exercise training, and weight loss provide significant clinical benefits and must be considered as the first line for treating both NAFLD and MS. Together, these results highlight the importance of multidisciplinary approach in early life [32
In fact, MS and NAFLD have been implicated in both disruption of neuroendocrine regulation of energy balance and accentuated inflammatory process, which may impair the benefits of weight loss therapy [6
]. Therefore, an important finding corroborating this hypothesis is that the balance between orexigenic and anorexigenic factors was improved, since a reduction in AgRP and increase in the alfa-MSH were observed in the present study. This was probably modulated by a significant reduction in the state of hyperleptinemia, a key hormone implicated in the central and peripheral control of energy balance [9
Moreover, a reduction of 27% of body fat, a significant reduction in visceral fat, subcutaneous fat, waist circumference, and an increase in the free fat mass was observed (). In support of this we showed a negative correlation between delta values of fat mass with free fat mass (R
= −0.75, P
= 0.001) (). Fujioka et al. showed that the decrease in the visceral/subcutaneous ratio and visceral fat was strongly correlated with the improvement in plasma glucose and lipid metabolism [36
]. Furthermore, Lee et al. showed that a reduction in body fat had significant effects on metabolic diseases, including cardiovascular disorders. Thus, this significant reduction in fat mass improves not only life expectancy but also significantly reduces the public sector costs associated with obesity related diseases [37
]. In addition, it is important to note that insulin resistance was decreased significantly in the study group (); however, the comparison between genders showed that the therapy was more effective to reduce insulin and HOMA-IR in males compared with female adolescents. However, the values of insulin and HOMA-IR were higher in male compared with female (data not shown).
On the other hand, the NPY and MCH were not improved. This may have occurred as a result of the percentage of weight loss (approximately 12% of their body mass), suggesting that these neuropeptides require a massive weight loss to favour changes in concentrations and improve the energy balance. In fact, it was shown previously in another study with obese adolescents that in the beginning of weight loss therapy the NPY concentration was increased as a compensatory adaptation and after a massive weight loss the NPY returns to basal values [39
]. The second hypothesis is that in this analysis, the ghrelin concentration was not changed, with the role of this orexigenic hormone in the upregulation of NPY being well established.
Moreover, the neuroendocrine regulation of energy balance is influenced by PAI-1, since it was demonstrated that this prothrombotic adipokine is involved in the response of NPY concentration in obese adolescents [35
]. This was confirmed in the present investigation by a positive correlation between delta values of PAI-1 with ghrelin concentration (R
= 0.68; P
= 0.002) (). Thus, another important finding in the present investigation was a reduction in PAI-1 and interleukin-6. Supporting this result, the adiponectin was significantly increased, favouring amelioration in the Lep/Adipo ratio, improving the control of subclinical inflammation, commonly associated with obesity.
The adiponectin concentration is a potent anti-inflammatory adipokine and acts in the regulation of insulin homeostasis, favouring the control of many chronic diseases, including atherosclerosis, hypertension, NAFLD, metabolic syndrome, cardiovascular diseases, thrombosis, and asthma [6
]. These data reinforce the importance of the results observed in the present study, mainly the reduction of hyperleptinemia and the increase in the adiponectinemia, promoting the decrease in the Lep/Adipo ratio. In addition, we showed a positive correlation between delta values of Lep/Adipo with fat mass and negative correlation between adiponectin with body mass and fat mass ().
Previously, it was shown that massive weight loss promoted an increase in adiponectin and adiponectin/leptin (A/L) ratio; additionally, a decrease in leptin levels and a reduction in exercise induced bronchospasm frequency and asthma-related symptoms, improving pro/anti-inflammatory adipokines. Furthermore, the leptin concentration was a predictor factor to explain changes in lung function, demonstrating the role of this adipokine in the inflammatory process, linking obesity and pulmonary disorders [7
]. Therefore, another significant finding in the present investigation was a reduction in the prevalence of asthma from 16% to 0%.
Interestingly, states of hyperleptinemia have also been implicated in the development of atherosclerosis [9
]. Supporting this, at the beginning of the intervention, 75% of the analysed obese adolescents presented a hyperleptinemia state; after intervention 55% remained in this condition, but both prevalence and median values of this adipokine were significantly decreased as mentioned above.
Although there was a significant improvement in the inflammatory state resulting from leptin reduction, leptin/adiponectin ratio, and increase in adiponectin, others important inflammatory markers such as TNF-α
, resistin, and CRP were not reduced. A possible explanation could be the presence of a hyperleptinemia state since 55% of the adolescents remained with high levels of leptin, even after significant reduction in concentration, suggesting that the neuroendocrine system could interpose in inflammatory process. However the complete understanding of the interplay between neuroendocrine regulations of energy balance and inflammation needs to be explored further. Reinforcing this hypothesis, Corgosinho et al. showed a positive correlation between PAI-1 and some orexigenic neuropeptides, such as the NPY, MCH, and the NPY/AgRP ratios suggesting that the impairment in the control of energy balance acts in a dependent manner, involving inflammatory processes [35
Some limitations need to be taken into account in interpretation of these findings. First, we had a dropout of 20% of the sample. The main reasons for dropping out in our study were financial and domestic, followed by education and job opportunities. Secondly, there is no control group in this study to compare with the normal states of cytokines and inflammation markers. Thirdly, a larger sample size is needed to better confirm the findings. However, the strengths of the current study include the assessment of a wider range of obesity comorbidities and parameters in a sample of obese adolescents undergoing interdisciplinary long-term therapy.
Finally, it is important to observe that obesity is estimated to reduce average of life expectancy and is imposing a major economic burden on health insurance [16
]. Increasing physical exercise and decreasing sedentary behaviour are a worldwide challenge. In fact, an American study aimed to increase physical activity among Latin adolescents through a school-based program has proved successful in decreasing sedentary behaviours. However the study group did not increase physical activity [42
]. Together, the results call for more initiatives from both public and private health insurance to challenge not only the control of obesity per se
but also the patterns of altered parameters which may impair the effect of multidisciplinary strategies in improving health.