The present study showed that long-term therapy was effective in reducing dietary fat intake and endotoxin levels. In addition, these data were positively correlated with improvements in insulin resistance in obese adolescents.
The chronic endotoxemia, have promoted glucose intolerance and hepatic insulin resistance, suggesting its role as a link between innate immunity, inflammation, and insulin resistance
Decreased endotoxin levels have been found with consumption of a low-fat diet compared with a high-fat diet
[28–30]. In addition, the type of fatty acid in the diet could have important effects on endotoxinemia. Recently, several studies have shown that omega-3 (ω-3) fatty acids, particularly eicosapentaenoic acid (EPA), reduces endotoxin and pro-inflammatory cytokine concentrations
[29, 30]. Moreover, Oz et al.
 demonstrated that a diet rich in EPA, docosahexaenoic acid (DHA), and prebiotic fructooligosaccharides (FOS) protects against LPS-induced systemic inflammatory responses. In contrast to the present study, Al-Attas et al.
 showed that a diet-controlled program in diabetic individuals did not significantly decrease endotoxin levels compared with individuals who only received insulin. Interestingly, herbs used in food dishes reduce the production of LPS and pro-inflammatory cytokines
. In the present study, we observed that interdisciplinary therapy was able to decrease the fat intake, which least in part, was sufficient to reduce endotoxin concentrations and insulin resistance. The reduced endotoxin levels to be related with recovery metabolism and inflammation status that leads to anti-inflammatory status.
The present study found a positive correlation between endotoxin and both pro-inflammatory cytokines (especially, IL-6) and insulin resistance. After interdisciplinary therapy, endotoxinemia, pro-inflammatory status and insulin resistance were decreased. These results showed the importance of making lifestyle changes (i.e., nutritional modification) to reduce the pro-inflammatory state in obese individuals. We have previously shown that long-term therapy is effective in reducing body fat (especially visceral fat), TNF-α and IL-6 and increasing IL-10 and adiponectin. In addition, we observed a positive correlation between pro-inflammatory cytokines (IL-6 and TNF-α levels) and visceral fat
. In addition, we can suggested a significant improvement of inflammatory profile once adiponectin, the anti-inflammatory adipokine, increased significantly after the long-term intervention (12%) and reduction of HOMA-IR, an index that present association to inflammatory pathways, such as increase of IL-6 and TNF-alpha.
Creely et al.
 found that circulating serum endotoxin was higher in type 2 diabetes mellitus (T2DM) patients than in lean healthy subjects, and endotoxin can activate the innate immune pathway in isolated abdominal adipocytes to stimulate secretion of pro-inflammatory cytokines. Creely et al.
 suggested that the subclinical inflammation seen in type 2 diabetes patients was related to the increase in endotoxin. Mehta et al.
 observed that endotoxemia (3 ng/kg intravenous bolus in healthy adults) induced an elevation in TNF-α and systemic insulin resistance in humans. Furthermore, insulin resistance measured at 24 h post-LPS was preceded by specific modulation of adipose inflammatory and insulin signaling pathways. Leuwer et al.
 have shown that endotoxemia leads to major increases in inflammatory adipokine (TNF-α, IL-6, and MCP-1) gene expression in white adipose tissue in mice. In addition, previous studies in human adipose tissue have shown that obesity and T2DM induce upregulation of inflammatory genes
. These results are in agreement with the present study in which endotoxin showed a close correlation with IL-6, which was reduced after 1 year of interdisciplinary therapy.
Although we did not directly analyze the effect of exercise, we cannot exclude that the exercise protocol used in the present study contributed to the beneficial effects of the interdisciplinary therapy in obese adolescents. Many studies
[11, 35–37] have actually demonstrated the benefits of exercise training, which induces an anti-inflammatory state in obese rat and human models. Bradley et al.
 suggested that voluntary exercise in diet-induced obese mice reduced adiposity despite continued consumption of a high-fat diet. In addition, exercise normalized insulin sensitivity and decreased adipose tissue inflammation (reduced IKK-β gene expression) in these obese mice. These data demonstrated the positive role of exercise training in preventing the development of several diseases, including obesity, diabetes, and fatty liver.
Starkie et al.
 demonstrated that an intravenous infusion of endotoxin induced a two to threefold increase in the plasma TNF-α level. When human subjects adopted an acute exercise protocol (75% VO2max), however, the production of TNF-α elicited by low-grade endotoxemia was inhibited. Similarly, Chen et al.
 found that chronically exercised rats exhibited minor pathological changes in the heart, liver, and lung after endotoxemia. In addition, Lira et al.
 observed that a lifestyle change associated with high-intensity, high-volume exercise induced favorable changes in chronic low-grade inflammatory markers and may reduce the risk for obesity, diabetes and cardiovascular diseases.
Although the small number of participants could be a limitation of the present study, the results contribute to the understanding of the mechanisms linking insulin resistance, adiponectinemia in obesity and endotoxemia to the inflammatory state. In addition, the present study highlights the importance of lifestyle interdisciplinary therapy intervention as clinical practice for obesity treatment.
In summary, the present study demonstrated an important association between dietary fat intake and endotoxin level, which reduced significantly after the long-term intervention. Indeed, based on these data, we can hypothesize a link between dietary fat intake, insulin resistance, endotoxin and inflammatory pathways. Taken together, these results suggest that interdisciplinary therapy is effective in decreasing inflammatory markers related to obesity.