The prevention of obesity and health concerns related to body fat is a major challenge worldwide. The aim of this study was to investigate the role of a medically supervised, multidisciplinary approach, on reduction in the prevalence of obesity related comorbidities, inflammatory profile, and neuroendocrine regulation of energy balance in a sample of obese adolescents. A total of 97 postpuberty obese adolescents were enrolled in this study. Body composition, neuropeptides, and adipokines were analysed. The metabolic syndrome was defined by the International Diabetes Federation (IDF). The abdominal ultrasonography was performed to measure visceral, subcutaneous fat and hepatic steatosis. All measures were performed at baseline and after one year of therapy. The multidisciplinary management promoted the control of obesity reducing body fat mass. The prevalence of metabolic syndrome, asthma, nonalcoholic fatty liver disease (NAFLD), binge eating, and hyperleptinemia was reduced. An improvement in the inflammatory profile was demonstrated by an increase in anti-inflammatory adiponectin and reduction in proinflammatory adipokines, plasminogen activator inhibitor-1, interleukin-6 concentrations, and in the Lep/Adipo ratio. Moreover, a reduction in the AgRP and an increase in the alfa-MSH were noted. The multidisciplinary approach not only reduced obesity but also is efficacious in cardiovascular risk factors, inflammatory profile, and neuroendocrine regulation of energy balance.
The prevalence of overweight and obesity has increased in many low- and middle-income countries [
In obese Brazilian adolescents it was observed that 27.16% present diagnoses of metabolic syndrome (MS). The most frequently altered parameter was HOMA-IR [
Obesity is a multifactor disease, resulting mainly from sedentary behaviours coupled with inadequate eating habits [
The overall result of a multifaceted obesity-management program, addressed by using multidisciplinary teams, in local and international literature is limited. The purpose of this study was to analyse the effects of a one-year weight loss approach on the control of obesity and related comorbidities, including metabolic profile, inflammatory markers, and neuroendocrine regulation of energy balance on a sample of obese adolescents within a medically supervised multidisciplinary obesity-management program.
Taking into consideration the multfactorial characteristics of obesity, a multidisciplinary therapy program was developed with the twin aims of combating the main trigger factors of obesity and increasing adherence to, as well as improving responses to, the treatment (Figure
Design conception of interdisciplinary therapy on obesity management in adolescents.
For this study, a sample of 97 postpuberty obese adolescents (56 girls and 41 boys) was engaged, with ages of 15–19 years, and the sampling method was a consecutive selection of the sample. The study was announced in the media on TV and radio and in journals and the adolescents were selected according to the inclusion and exclusion criteria of the study. The adolescents of this study had the same level of education and mainly belonged to the same social class and ethnicity. These adolescents were recruited from São Paulo, Brazil, and the program ran from January to December during three consecutive years.
Inclusion criteria were tanner stage five [
Only the adolescents who had compliance of 75% in all sections of the therapy were included in the analyses. The main reasons for dropping out
Weight was measured by the plethysmography scale (BODPOD equipment) where patients wore the minimum clothing possible and height was measured using a stadiometer (Sanny, model ES 2030). After obtaining the data, body mass index (BMI) was calculated by dividing the weight by height squared (kg/m2). Body composition, including body fat (percentage and kilograms) and lean mass (percentage and kilograms), was obtained through air displacement plethysmography (BODPOD).
Blood samples were collected at the outpatient clinic at approximately 8:00 a.m. after an overnight fast (12 hours). Insulin resistance was assessed by the homeostasis model assessment insulin resistance index (HOMA-IR). HOMA-IR was calculated using the FBG and the immune-reactive insulin (I): (FBG (mg/dL)
The adipokines concentrations were measured using commercial immunoassay kits eBioscience (San Diego, CA, USA) and R&D Systems (Minneapolis, MN, USA) according to manufacturers’ manual. The reference values for leptin have been previously described by Gutin et al. [
The abdominal ultrasonography (US) procedures and the measurements of visceral and subcutaneous fat tissue and fatty liver were performed by the same physician at the baseline time point and following 1 year of therapy. This physician was a specialist in imaging diagnostics. A 3.5-MHz multifrequency transducer (broad band) was used to reduce the risk of misclassification. The intraexamination coefficient of the variation for abdominal US was 0.8%. US measurements of intra-abdominal (visceral) and subcutaneous fat were obtained. US-determined subcutaneous fat was defined as the distance between the skin and external face of the rectus abdominal muscle, and visceral fat was defined as the distance between the internal face of the same muscle and the anterior wall of the aorta. The cut-off points for the definition of visceral obesity by ultrasonography were based on the previous methodological descriptions [
Steatosis evaluation was performed by abdominal ultrasonography. The definition of ultrasonic fatty liver was based on previously reported diagnostic criteria and detected liver steatosis was classified as grade 1 (liver attenuation slightly less than spleen); grade 2 (more pronounced difference between liver and spleen and intrahepatic vessels not seen or slightly higher attenuation than liver); grade 3 (markedly reduced liver attenuation with a sharp contrast between liver and intrahepatic vessels) [
Adolescents underwent a diagnostic clinical evaluation for general health (family history and obesity) and sexual maturation was also assessed. Subsequently, adolescents were examined monthly. Metabolic syndrome was defined using International Diabetes Federation criteria: a waist circumference (WC) greater than 80 cm for girls and 94 cm for boys, high-density lipoprotein (HDL) values ≤50 mg/dL for girls and ≤40 mg/dL for boys, concentrations of triglycerides (TG) higher than 150 mg/dL, blood glucose levels higher than 100 mg/dL, and blood pressures ≥130/85 mmHg [
During the intervention (1 year), adolescents followed a program of combined training (aerobic/resistance exercise) which included sessions of 60 minutes (30 min aerobic and 30 min resistance) with a frequency of three times a week (180 minutes/week), under the supervision of an exercise physiologist. The aerobic training program was established based on a cardiopulmonary exercise test. The intensity of aerobic training was fixed at the load corresponding to the first ventilatory threshold (50%–70% of oxygen consumption test). During every session of aerobic exercise, heart rate was monitored by a frequency counter. Resistance training was divided into two types, wave (with loads of repeats 15–20, 10–12 and 6–8) and linear (20 replicates), based on exercises that covered large muscle groups of both lower and upper limbs. The program follows the recommendations given by the American College of Sports Medicine [
Food consumption was set at the recommended levels of dietary intake for individuals with low levels of physical activity, based on age, gender, and a balanced diet [
The caloric content was estimated using Dietary Reference Intakes equations, according to low levels of physical activity, based on age and patient gender. The distribution of macronutrients was fat (25–35%), carbohydrate (45–65%), and protein (10–30%). It is important to highlight that food quality was also assessed during nutrition intervention [
Diagnoses of psychological problems most commonly associated with obesity, such as depression, body image concerns, anxiety, and lower self-esteem, were assessed through validated questionnaires. During long-term intervention, adolescents were followed up weekly in the one year therapy support group, and if necessary, individual psychological therapy was recommended when behavioural alterations were found (data not shown).
During psychological therapy, all adolescents completed the Portuguese versions of the BES to verify the symptoms of binge eating and BITE to verify Bulimia symptoms, including the purgative subtype (Figure
Methodological description.
The data are presented as the mean ± standard deviation (SD), and
The interdisciplinary management promoted obesity control, reducing the prevalence of metabolic syndrome, nonalcoholic fatty liver diseases, asthma, insulin resistance, and eating disorders, including symptoms of bulimia nervosa and binge eating disorder (Table
Prevalence of metabolic disorders associated with obesity.
Variables | Baseline (%) | After therapy (%) |
|
|
---|---|---|---|---|
Metabolic syndrome factors (IDF classification) | Glucose | 13 | 5 | <0.001 |
Insulin | 23 | 4 | <0.001 | |
Triglyceride | 17 | 7 | <0.001 | |
HDL-cholesterol | 42 | 31 | 0.30 | |
Systolic blood pressure | 26 | 5 | <0.001 | |
Diastolic blood pressure | 14 | 2 | <0.001 | |
Waist circumference | 62 | 14 | <0.001 | |
| ||||
MS |
Metabolic syndrome | 30 | 2 | <0.001 |
Nonalcoholic fatty liver disease | 33 | 10 | <0.001 | |
| ||||
Others complications | HOMA-IR | 83 | 40 | <0.001 |
Hyperleptinemia | 75 | 55 | <0.001 | |
Asthma | 16 | 0 | <0.001 | |
Binge eating | 6 | 2 | <0.001 |
Statistical significance
Prevalence of obesity complications: (a) metabolic syndrome factors; (b) comorbidities associated with obesity; *statistical significance,
A significant reduction in the body mass, fat mass, visceral fat, subcutaneous fat, waist circumference, and blood pressure was shown. These data were associated with an increased fat free mass, demonstrating an improvement in most risks related to obesity, after one year of interdisciplinary therapy (Table
Effects of interdisciplinary therapy in body composition.
Variables | Baseline | After therapy |
|
Δ value |
---|---|---|---|---|
Body mass (kg) |
|
|
<0.001 |
|
Height (m) |
|
|
0.07 |
|
BMI (kg/m²) |
|
|
<0.001 |
|
Fat mass (kg) |
|
|
<0.001 |
|
Fat mass (%) |
|
|
<0.001 |
|
Free fat mass (kg) |
|
|
<0.001 |
|
Free fat mass (%) |
|
|
<0.001 |
|
Visceral fat (cm) |
|
|
<0.001 |
|
Subcutaneous fat (cm) |
|
|
<0.001 |
|
Waist circumference (cm) |
|
|
<0.001 |
|
Systolic blood pressure (mmHg)* | 120 (100–190) | 110 (100–140) | <0.001 | −10.00 (−70–20) |
Diastolic blood pressure (mmHg)* | 80 (70–110) | 70 (60–90) | <0.001 | 0.00 (−40–10) |
Other important results observed in the present study were the statistical reduction in insulin, triglyceride, LDL, and VLDL cholesterol concentrations. On the other hand, HDL concentration and insulin resistance index (HOMA-IR) were improved (Table
Effects of interdisciplinary therapy in metabolic profile (factors associated with metabolic syndrome definition by International Diabetes Federation (IDF)).
Variables | Baseline | After therapy |
|
Δ value |
---|---|---|---|---|
Waist circumference (cm) |
|
|
<0.001 |
|
Glucose (mg/dL) |
|
|
0.43 |
|
Insulin (µU/mL) |
|
|
<0.001 |
|
HDL-cholesterol (mg/dL) |
|
|
<0.001 |
|
LDL-cholesterol (mg/dL) |
|
|
<0.001 |
|
VLDL-cholesterol (mg/dL) |
|
|
<0.001 |
|
Triglyceride (mg/dL) |
|
|
<0.001 |
|
HOMA-IR |
|
|
<0.001 |
|
HOMA-IR: homeostasis model assessment insulin-index resistance; HLD: high-density lipoprotein; LDL: low-density lipoprotein; VLDL: very-low-density lipoprotein. Reference values: glucose (60–110 mg/dL); insulin (<20
In addition, the weight loss therapy promoted an improvement in the markers of neuroendocrine regulation of energy balance, including a significant reduction in the orexigenic factor AgRP, as well as an increase in the anorexigenic factor
Effects of interdisciplinary therapy in neuroendocrine regulation of energy balance and inflammatory profile.
Variables | Baseline | After therapy |
|
Δ value | |
---|---|---|---|---|---|
Neuroendocrine regulation of energy balance | AgRP (ng/mL) |
|
|
<0.001 |
|
NPY (ng/mL) |
|
|
0.66 |
|
|
NPY/AgRP ratio* | 0.41 (0.03–9.1) | 0.42 (0.01–5.33) | 0.07 | 0.02 (−2.47–2.86) | |
MCH (ng/mL) |
|
|
0.80 |
|
|
|
|
|
0.03 |
|
|
Ghrelin (ng/mL) |
|
|
0.40 |
|
|
Leptin (ng/mL) |
|
|
<0.001 |
|
|
| |||||
Inflammatory profile | Adiponectin (µg/L) |
|
|
<0.001 |
|
Lep/Adipo ratio* | 5.7 (0.15–44.3) | 3.7 (0.16–30.9) | <0.001 | −10.48 (5.64–36.41) | |
TNF- |
|
|
0.23 |
|
|
CRP (ng/mL) |
|
|
0.48 |
|
|
Resistin (ng/mL) |
|
|
0.71 |
|
|
PAI-1 (ng/mL) |
|
|
<0.001 |
|
|
interleukin-6 (IL-6) |
|
|
0.05 |
|
The inflammatory profile was improved as demonstrated by an increase in the concentration of anti-inflammatory adipokine adiponectin, and a reduction in the proinflammatory adipokines, including plasminogen activator inhibitor-1 and interleukin-6 concentrations. Moreover, the hyperleptinemia was reduced and leptin/adiponectin ratio was improved. However, no changes in TNF-alpha, CRP, and resistin concentrations were observed (Table
Finally, in the correlation analysis of the delta values
Correlations analysis.
Variables (Δ values) |
|
|
|
---|---|---|---|
Fat mass (kg) | Free fat mass (%) | −0.75 | 0.001 |
Adiponectin (µg/L) | −0.72 | 0.001 | |
Lep/Adipo ratio | 0.67 | 0.003 | |
Visceral fat (cm) | −0.57 | 0.871 | |
| |||
Subcutaneous fat (cm) | Fat mass (%) | 0.71 | 0.002 |
Free fat mass (%) | −0.71 | 0.002 | |
| |||
Adiponectin (µg/L) | Body mass (kg) | −0.65 | 0.003 |
Visceral fat (cm) | −0.20 | 0.571 | |
HOMA-IR | −0.20 | 0.873 | |
| |||
PAI-1 (ng/mL) | Ghrelin (ng/mL) | 0.68 | 0.002 |
| |||
Visceral fat (cm) | HOMA-IR | 0.67 | 0.572 |
Fat mass (%) | −0.28 | 0.421 |
Lep/Adipo ratio: leptin/adiponectin ratio; PAI-1: plasminogen activator inhibitor-1; HOMA-IR: homeostasis model assessment insulin index-resistance; statistical significance
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 [
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 [
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 (Table
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 [
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 [
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 [
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 [
Interestingly, states of hyperleptinemia have also been implicated in the development of atherosclerosis [
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-
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 [
The multidisciplinary approach reduced not only obesity but also the prevalence of metabolic syndrome, NAFLD, asthma, inflammatory markers, and cardiovascular risk. Moreover, an improvement in the neuroendocrine regulation of energy balance was observed. Finally, the design of a type of therapy that favours better adherence is a challenge, considering the complexity of this disease and the possibility of increasing quality and life expectation.
The authors have no financial relationships relevant to this paper to disclose.
There is no conflict of interests that could be perceived as prejudicing the impartiality of the research reported.
The authors would like to thank all the volunteers of this research, the CEPE for all their support, and the sources of funding: FAPESP (2006/00684-3, 2008/53069-0, 2011/50356-0, 2011/50414-0), FAPESP (CEPID/Sleep no. 9814303-3 S.T), AFIP, CNPq, FADA, CAPES-PNPD 2566/2011, and Universidade Federal de São Paulo.