Cancer as a Proinflammatory Environment: Metastasis and Cachexia.

The development of the syndrome of cancer cachexia and that of metastasis are related with a poor prognostic for cancer patients. They are considered multifactorial processes associated with a proinflammatory environment, to which tumour microenvironment and other tissues from the tumour bearing individuals contribute. The aim of the present review is to address the role of ghrelin, myostatin, leptin, HIF, IL-6, TNF-α, and ANGPTL-4 in the regulation of energy balance, tumour development, and tumoural cell invasion. Hypoxia induced factor plays a prominent role in tumour macro- and microenvironment, by modulating the release of proinflammatory cytokines.

Resistência insulínica pode prejudicar a redução da espessura mediointimal em adolescentes obesos / Insulin resistance can impair reduction on carotid intima-media thickness in obese adolescents

FUNDAMENTO: O processo aterosclerótico no nível endotelial começa em idade precoce e parece estar associado com a obesidade e suas comorbidades como a resistência insulínica. OBJETIVO: O objetivo deste estudo foi verificar a influência da resistência insulínica em marcadores inflamatórios e subclínicos de aterosclerose em adolescentes obesos. MÉTODOS: Sessenta e seis adolescentes obesos pós-púberes foram divididos em dois grupos de acordo com o índice de resistência insulínica estimado pelo Modelo de Avaliação da Homeostase (HOMA-RI): com resistência insulínica (RI) n = 39 e sem resistência insulínica (NRI) n = 27, e foram submetidos a uma intervenção interdisciplinar ao longo de um ano. A espessura mediointimal da artéria carótida comum (EMIC), e o tecido adiposo visceral e subcutâneo foram determinados por ultrassonografia. A composição corporal, pressão arterial, índice HOMA-RI, perfil lipídico e as concentrações de adipocinas [leptina, adiponectina, e inibidor do ativador do plasminogênio-1 (PAI-1)] foram analisados antes e após a terapia. RESULTADOS: Ambos os grupos apresentaram melhoras significativas na composição corporal, estado inflamatório (redução da concentração de leptina e PAI 1; aumento de adiponectina plasmática) e redução da EMIC. Apenas o grupo NRI mostrou correlação positiva entre as alterações na gordura visceral (∆Visceral) e mudanças na EMIC (∆ EMIC) (r = 0,42, p < 0,05). A análise por regressão linear simples revelou o ∆Visceral ser um preditor independente para a redução da EMIC nesse grupo (R2 ajustado = 0,14, p = 0,04). Os valores finais da EIMC permaneceram significativamente maiores no grupo RI, quando comparado com grupo NRI. CONCLUSÃO: A presença de resistência insulínica pode prejudicar mudanças na EMIC levando ao desenvolvimento precoce da aterosclerose em adolescentes obesos submetidos a uma intervenção interdisciplinar.

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Long-term interdisciplinary therapy reduces endotoxin level and insulin resistance in obese adolescents.

AIM: The purpose of the present study was to assess the dietary fat intake, glucose, insulin, Homeostasis model assessment for insulin resistance HOMA-IR, and endotoxin levels and correlate them with adipokine serum concentrations in obese adolescents who had been admitted to long-term interdisciplinary weight-loss therapy. DESIGN: The present study was a longitudinal clinical intervention of interdisciplinary therapy. Adolescents (n = 18, aged 15-19 y) with a body mass index > 95th percentile were admitted and evaluated at baseline and again after 1 year of interdisciplinary therapy. We collected blood samples, and IL-6, adiponectin, and endotoxin concentrations were measured by ELISA. Food intake was measured using 3-day diet records. In addition, we assessed glucose and insulin levels as well as the homeostasis model assessment for insulin resistance (HOMA-IR). RESULTS: The most important finding from the present investigation was that the long-term interdisciplinary lifestyle therapy decreased dietary fat intake and endotoxin levels and improved HOMA-IR. We observed positive correlations between dietary fat intake and endotoxin levels, insulin levels, and the HOMA-IR. In addition, endotoxin levels showed positive correlations with IL-6 levels, insulin levels and the HOMA-IR. Interestingly, we observed a negative correlation between serum adiponectin and both dietary fat intake and endotoxin levels. CONCLUSIONS: The present results indicate an association between dietary fat intake and endotoxin level, which was highly correlated with a decreased pro-inflammatory state and an improvement in HOMA-IR. In addition, this benefits effect may be associated with an increased adiponectin level, which suggests that the interdisciplinary therapy was effective in improving inflammatory pathways.

Influence of visceral and subcutaneous fat in bone mineral density of obese adolescents / A influência da gordura visceral e subcutânea na densidade mineral óssea de adolescentes obesos

OBJECTIVE: To verify the influence of visceral and subcutaneous fat, as well adipokines in bone mineral density (BMD) in obese adolescents. SUBJECTS AND METHODS: The study involved 125 postpubertal obese adolescents (45 boys and 80 girls). Anthropometric measurements, body composition, visceral and subcutaneous fat, and BMD were determined. Leptin, adiponectin, and insulin levels also analyzed. RESULTS: Data demonstrated a negative relationship between BMD with insulin resistance, visceral fat and leptin concentration; and bone mineral content with visceral/subcutaneous ratio. Positive association between BMD and subcutaneous fat was observed. CONCLUSIONS: Visceral fat and insulin resistance, as well as visceral/subcutaneous ratio and leptin concentration, were negative predictors of BMD in boys and girls, respectively. However, subcutaneous fat had a protective influence in BMD only in boys.

OBJETIVO: Verificar a influência da gordura visceral e subcutânea, assim como das adipocinas na densidade mineral óssea (DMO) em adolescentes obesos. SUJEITOS E MÉTODOS: O estudo envolveu 125 adolescentes obesos pós-púberes. Medidas antropométricas, composição corporal, gordura visceral e subcutânea e DMO foram determinadas. Níveis de leptina, adiponectina e insulina foram analisados. RESULTADOS:Os dados demonstraram associação negativa entre DMO com resistência insulínica, gordura visceral e concentração de leptina; e conteúdo mineral ósseo com a razão visceral/subcutânea. Associação positiva entre DMO e gordura subcutânea foi observada. CONCLUSÕES: Gordura visceral, resistência insulínica, razão visceral/subcutânea e concentração de leptina foram preditores negativos da DMO em meninos e meninas, respectivamente. Entretanto, a gordura subcutânea demonstrou exercer influência positivamente na DMO somente nos meninos.

Alterations in downstream mediators involved in central control of eating behavior in obese adolescents submitted to a multidisciplinary therapy.

OBJECTIVE: The aim of this study was to verify the effects of a multidisciplinary therapy (24 weeks) on neurohormonal control of food intake, specifically in orexigenic (total ghrelin, agouti-related protein [AgRP], neuropeptide Y [NPY], and melanin-concentrating hormone) and anorexigenic factors (leptin, insulin, and alpha-melanocyte stimulating hormone [α-MSH]), in obese adolescents. METHODS: A total of 88 adolescents (38 boys and 50 girls), including 62 obese and 26 normal-weight, aged 15-19 years were recruited. Obese adolescents were submitted to a 24-week multidisciplinary therapy. AgRP, NPY, melanin-concentrating hormone, leptin, insulin, glucose, α-MSH, total ghrelin, and food intake were measured at three stages (at baseline, after 12 weeks, and after 24 weeks). RESULTS: At baseline, obese adolescents showed hyperleptinemia (circulating leptin levels, which were, in boys and girls, 40 and 35 times higher than in normal-weight subjects, respectively). After 24 weeks, these values decreased in all obese patients. Our results showed no differences in ghrelin levels between obese and normal-weight adolescents, in both genders. However, obese boys reduced their plasma ghrelin concentration after 24 weeks of therapy (p < .05). The multidisciplinary therapy decreased NPY and AgRP values and increased α-MSH; simultaneously with these changes there was a decrease in total food intake after 24 weeks of therapy. CONCLUSIONS: We can conclude that the multidisciplinary therapy was efficient to modulate neurohormonal control of food intake in obese adolescents.

Visceral fat decreased by long-term interdisciplinary lifestyle therapy correlated positively with interleukin-6 and tumor necrosis factor-α and negatively with adiponectin levels in obese adolescents.

The purpose of this study was to assess the level of cytokine expression in correlation with visceral and subcutaneous fat in obese adolescents admitted to long-term interdisciplinary weight loss therapy. The study was a longitudinal clinical intervention of interdisciplinary therapy. Adolescents (18, aged 15-19 years) with body mass indexes greater than the 95th percentile were admitted and evaluated at baseline and again after 1 year of interdisciplinary therapy. Visceral and subcutaneous fat was analyzed by ultrasonography. Blood samples were collected to analyze tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), and adiponectin concentrations that were measured by enzyme-linked immunosorbent assay. The most important finding in the present investigation is that the long-term interdisciplinary lifestyle therapy decreased visceral fat. Positive correlations between IL-6 levels and visceral fat (r = 0.42, P < .02) and TNF-α levels and visceral fat (r = 0.40, P < .05) were observed. Negative correlations between TNF-α levels and subcutaneous fat (r = -0.46, P < .01) and adiponectin levels and subcutaneous fat (r = -0.43, P < .03) were also observed. In addition, we found a positive correlation between TNF-α levels and the visceral to subcutaneous fat ratio (r = 0.42, P < .02) and a negative correlation between adiponectin level and the visceral to subcutaneous fat ratio (r = -0.69, P < .001). Despite the limitation of sample size, our results indicate that the observed massive weight loss (mainly visceral fat) was highly correlated with a decreased inflammatory state, suggesting that the interdisciplinary therapy was effective in decreasing inflammatory markers.

Quality of life in Brazilian obese adolescents: effects of a long-term multidisciplinary lifestyle therapy.

BACKGROUND: Obesity has adverse physical, social, and economic consequences that can negatively affect quality of life (QOL). Thus the aim of this study was to verify the effects of a long-term multidisciplinary lifestyle intervention on QOL, body image, anxiety, depression and binge eating in obese adolescents. METHODS: Sixty-six obese adolescents (41 girls and 25 boys; BMI: 35.62 +/- 4.18 kg/m2) were recruited from the Multidisciplinary Obesity Intervention Program outpatient clinic, and were submitted to a multidisciplinary lifestyle therapy (short-term = 12 weeks and long-term = 24 weeks), composed of medical, dietary, exercise and psychological programs. Validated self-report questionnaires were used to assess symptoms of anxiety Trait/State (STAI); depression (BDI); binge eating (BES), body image dissatisfaction (BSQ) and QOL (SF-36). Data were analyzed by means of scores; comparisons were made by ANOVA for repeated measures, and Turkey's test as post-hoc and Students T test. RESULTS: Long-term therapy decreased depression and binge eating symptoms, body image dissatisfaction, and improved QOL in girls, whereas, for boys, 24 weeks, were effective to reduce anxiety trait/state and symptoms of binge eating, and to improve means of dimensions of QOL (p < .05). CONCLUSION: A long-term multidisciplinary lifestyle therapy is effective to control psychological aspects and to improve QOL in obese adolescents.

Efeitos da terapia multidisciplinar de longo prazo sobre a composição corporal de adolescentes internados com obesidade severa / Effects of long-term multidisciplinary inpatient therapy on body composition of severely obese adolescents

OBJETIVO: Descrever os efeitos da terapia multidisciplinar de longo prazo sobre a composição corporal de adolescentes obesos severos internados. MÉTODOS: Um total de 728 adolescentes obesos extremos, incluindo 249 meninos (15,25±1,56 anos) e 479 meninas (15,34±1,59 anos), recebeu terapia multidisciplinar durante um período de 3 a 9 meses. A terapia consistiu de redução da ingestão energética, orientação dietética, exercícios físicos e terapia psicológica. A composição corporal foi analisada pela bioimpedância elétrica, e a aptidão física foi avaliada pelo teste em ciclo ergômetro multiestágios. O tipo e duração de cada atividade foram avaliados através de recordatório diário de atividade física. RESULTADOS: Foi verificada redução significante (p < 0,05) na massa corporal (27,84±12,49 kg para meninos e 21,60±9,87 kg para meninas), índice de massa corporal (9,19±3,88 kg/m² para meninos e 7,72±3,98 kg/m² para meninas) e da gordura corporal. Além disso, a porcentagem de massa magra aumentou significantemente (p < 0,05) nos meninos (de 58,8±6,41 para 69,98±7,43 por cento) e nas meninas (de 51,86±4,96 para 60,04±5,65 por cento). CONCLUSÃO: A terapia multidisciplinar de longo prazo permite reduzir acentuadamente a obesidade severa, preservando o crescimento e a porcentagem de massa magra.

OBJECTIVE: To describe the effects of long-term multidisciplinary inpatient therapy on body composition of severely obese adolescents. METHODS: A total of 728 extremely obese adolescents, including 249 boys (aged 15.25±1.56 years) and 479 girls (aged 15.34±1.59 years) received multidisciplinary therapy during a period of 3 to 9 months. The therapy consisted of reduced energy intake, dietetic education, physical exercises and psychological therapy. Body composition was assessed by bioelectrical impedance analysis, and physical capacity was assessed by the multistage cycle ergometer test. Type and duration of each activity were recorded using a daily controlled activity diary. RESULTS: There was a significant decrease (p < 0.05) in body mass (27.84±12.49 kg for boys and 21.60±9.87 kg for girls), body mass index (9.19±3.88 kg/m² for boys and 7.72±3.98 kg/m² for girls) and fat mass. In addition, the percentage of fat free mass increased significantly (p < 0.05) in boys (from 58.8±6.41 to 69.98±7.43 percent) and in girls (from 51.86±4.96 to 60.04±5.65 percent). CONCLUSION: Long-term multidisciplinary approach allows significant reduction in severe obesity, preserving growth and percentage of fat free mass.

Plaqueta e leptina em adolescentes com obesidade / Platelet and leptin in obese adolescents

OBJETIVOS: Analisar a influência de obesidade na contagem de células imunológicas e na concentração dos hormônios cortisol e leptina, a fim de estabelecer uma relação entre as variáveis analisadas. MÉTODOS: Foram recrutados 27 adolescentes obesos [índice de massa corporal (IMC) ≥ percentil 95[ e 21 não-obesos (IMC ≤ percentil 75), de ambos os sexos, com idade entre 15 e 19 anos, na fase pós-púbere. O IMC foi calculado através da divisão do peso pela altura ao quadrado e a composição corporal foi estimada por pletismografia no sistema Bod PodTM. Amostras de sangue foram colhidas para análise de leucócitos, neutrófilos, linfócitos, monócitos, plaquetas, cortisol e leptina. O teste de Kolmogorov-Smirnov foi utilizado, seguido pelo teste t de Student independente supondo distribuição normal. O nível de significância estabelecido foi p < 0,05 e expresso como média ± desvio padrão. Os dados foram analisados utilizando o programa SPSS para Windows versão 12.0. RESULTADOS: Não houve diferença entre o grupo obeso e o não-obeso na concentração sérica de leucócitos, neutrófilos, linfócitos, monócitos e cortisol. O grupo de adolescentes obesos apresentou maiores concentrações de plaquetas e leptina (p < 0,01). A prevalência de hiperleptinemia foi de 25,92 por cento nos adolescentes obesos (15,38 por cento, sexo masculino e 35,7 por cento, feminino). CONCLUSÕES: Os adolescentes obesos apresentaram maiores concentrações de plaquetas e leptina em comparação aos não-obesos. Observou-se que as adolescentes obesas apresentaram maior prevalência de hiperleptinemia do que os adolescentes obesos.

OBJECTIVE: To analyze the influence of obesity status on immune cell count and concentration of the hormones cortisol and leptin, in order to establish a relationship among the variables analyzed. METHODS: We recruited 27 obese [body mass index (BMI) ≥ 95th percentile[ and 21 non-obese (BMI ≤ 75th percentile) adolescent boys and girls, aged 15-19 years at the post-pubertal stage. BMI was calculated as body weight divided by height squared, and body composition was estimated by plethysmography in the Bod PodTM system. Blood samples were collected to analyze leukocytes, neutrophils, lymphocytes, monocytes, platelets, cortisol, and leptin. The Kolmogorov-Smirnov test was performed, followed by the independent Student t test in case of normal distribution. Significance values were set at p < 0.05 and expressed as means ± standard deviation. The statistical package SPSS for Windows version 12.0 was used. RESULTS: There was no difference between obese and non-obese adolescents in terms of leukocyte, neutrophil, lymphocyte, monocyte and cortisol serum concentrations. The group of obese adolescents presented higher platelet and leptin concentrations (p < 0.01). The prevalence of hyperleptinemia was 25.92 percent in the obese adolescents (15.38 percent in boys and 35.7 percent in girls). CONCLUSIONS: Obese adolescents have higher platelet and leptin concentrations in comparison with non-obese adolescents. It was also found that obese girls presented a higher prevalence of hyperleptinemia than obese boys.