Biomarcadores inflamatórios e determinantes da síndrome metabólica em adultos jovens saudáveis
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2012-02-03
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Universidade Federal de Viçosa
Resumo
Várias doenças crônicas são acompanhadas por processos inflamatórios e evidências continuam a se acumular sobre a relevância clínica dos preditores laboratoriais destes eventos fisiopatológicos. Neste contexto, o presente estudo se propôs a avaliar, em indivíduos jovens e clinicamente saudáveis, as concentrações plasmáticas de TNF-α e IL-6 e a expressão de genes relacionados ao processo inflamatório (TNF-α, IL-6, ICAM1, IL1R1 e IL-18) e suas possíveis associações com fatores de risco para o desenvolvimento da síndrome metabólica (SM). Foram avaliados 161 indivíduos quanto à antropometria, composição corporal, ingestão dietética, além de dados bioquímicos e clínicos. A dosagem plasmática de TNF-α e IL-6 foi realizada por ensaio imunológico (ELISA) em plasma EDTA. A expressão gênica (EG) relativa foi feita em células mononucleares (PBMC) utilizando-se PCR em tempo real. As comparações entre grupos foram feitas mediante os testes de Mann-Whitney-U ou Student-t, de acordo com a distribuição das variáveis. Foram utilizados a correlação de Spearman e modelos de regressão linear e logística rastrear associações e fatores preditivos relativos aos biomarcadores e aos componentes da SM. Os resultados foram apresentados como média ± DP com intervalo de confiança de 95% e nível de significância estatística de P<0,05. Os resultados revelaram que as concentrações plasmáticas de TNF-α e IL-6 foram superiores nos indivíduos do sexo masculino (P<0,001), contrariamente aos valores de EG que não se diferenciaram entre os gêneros. Os indivíduos com maiores níveis circulantes (MNC) de TNF-α também apresentaram maiores valores de peso corporal, perímetro da cintura, relação cintura/quadril, massa livre de gordura, pressão arterial sistólica e diastólica, glicose e ácido úrico sanguíneos e por outro lado, menores valores da % de gordura total, colesterol total e frações HDL-c e LDL-c (P<0,05). Já os indivíduos com MNC de IL-6 demonstraram maiores valores de peso corporal, IMC, gordura troncular, massa livre de gordura, pressão arterial sistólica e diastólica, fração HDL-c e ácido úrico, por outro lado, menores valores de % de gordura total, pregas cutâneas tricipital e bicipital, triacilgliceróis, colesterol total e fração LDL-c (P<0,05). A EG desta citocina se apresentou de forma inversa às concentrações plasmáticas de IL-6 (P=0,03). Indivíduos com MNC de TNF-α consumiam mais calorias, proteínas, cobre e fibras, no entanto menos ferro na dieta (P<0,05). Já aqueles com MNC de IL-6 consumiam mais calorias,macronutrientes, fibras, ferro e cobre (P<0,05). Mediante análise de regressão simples, observou-se que a EG de ICAM1, do IL1R1 e da IL-18 tiveram efeito preditivo positivo sobre os níveis circulantes de TNF-α (P< 0,05). Os indivíduos que se posicionaram nos dois maiores tercis (3,48 a 5,08 pg/mL e ≥ 5,09 pg/mL) da distribuição dos níveis circulantes do TNF-α, quando comparados àqueles no menor tercil, demonstraram aumento importante nas chances de apresentar obesidade abdominal (P<0,05). Da mesma forma, aqueles que se posicionaram no maior tercil, quando comparados àqueles no menor, demonstraram aumento importante nas chances de apresentar níveis reduzidos deHDL-c. Quando a mesma análise foi feita para IL-6, verificou-se que os indivíduos que se posicionaram nos dois maiores tercis (3,43 a 4,86 pg/mL e ≥ 4,87 pg/mL) da distribuição dos níveis circulantes desta citocina, quando comparados àqueles no menor tercil, mostraram aumento importante nas chances de apresentar concentrações séricas diminuídas de HDL-c. Este estudo contribuiu para o melhor entendimento das associações entre os marcadores de interesse e os fatores de risco para a ocorrência das doenças associadas à SM. E ainda, evidenciou a associação da EG de alguns marcadores inflamatórios em PBMC com variáveis importantes no contexto das doenças metabólicas, mesmo em adultos saudáveis.
Several chronic diseases are accompanied by inflammatory processes and evidence continues to accumulate on the clinical relevance of these laboratory predictors of pathophysiological events. In this context, the present study was to evaluate, in young and clinically healthy individuals, plasma concentrations of TNF- and IL-6 and the expression of genes related to inflammation (TNF-α, IL-6, ICAM1, IL1R1 and IL-18) and their possible association with risk factors for the development of metabolic syndrome (MS). 161 individuals were evaluated about the anthropometry, body composition, dietary intake, and biochemical and clinical datas. The plasma level of TNF-α and IL-6 was conducted by immunoassay (ELISA) in EDTA plasma. Gene expression (GE) was performed on periferial blood mononuclear cells (PBMC) using real time PCR. Comparisons between groups were performed by the Mann-Whitney-U or Student-t in accordance with the distribution of variables. We used Spearman correlation, the linear regression model and the logistic regression. The results were presented as mean ± SD, interval of 95% and significance level of P <0.05. The results showed that plasma concentrations of TNF-α and IL-6 were higher in males (P <0.001), contrary to the values of GE was not different between genders. Individuals with higher circulating levels of TNF-α also showed higher body weight, waist circumference, waist/hip ratio, fat-free mass, systolic and diastolic blood pressure, glucose and uric acid levels, and on the other hand, smaller values of percentage of total fat, total cholesterol and HDL- and LDL-c (P <0.05). Individuals with higher circulating levels of IL-6 showed higher values of body weight, BMI, truncal fat, fat-free mass, systolic and diastolic blood pressure, HDL-c and uric acid, on the other hand, lower values of percentage of total fat, biceps and triceps skinfold, triglycerides, total cholesterol and LDL-c (P <0.05). The GE of this cytokine presented inverse concentrations of IL-6 in the plasm (P = 0.03). Individuals with higher TNF-α consumed more calories, protein, copper and fiber, but less iron in the diet (P<0.05). Those with higher IL-6 consumed more calories, macronutrients, fiber, iron and copper (P<0.05). By simple regression analysis, we found that the GE of ICAM1, the R1IL- 1 and IL-18 had a positive predictive effect on circulating levels of TNF-α (P<0.05 ). As for IL-6, body weight, fat-free mass, truncal adiposity, the systolic and diastolic blood pressure, levels of uric acid, glucose and LDL-c had a positive predictive effect, unlike percentage of total fat, circulating levels of total cholesterol and LDL-c and HDL-c, besides the concentration of selenium in nails, which had a negative predictive effect. Individuals who are positioned in the two last tertiles (3.48 to 5.08 pg / mL and ≥ 5.9 pg / mL) of the distribution of circulating levels of TNF-α, compared with those in the lowest tertile (<3.48 pg/mL) showed a significant increase the chances of having abdominal obesity (P <0.05). In the same way, those who werw in the last tertile, compared with those in smaller, showed a significant increase in the chances of having low levels of HDL-c. When the same analysis was performed for IL-6, it was found that individuals who were in the two largest tertiles (3.43 to 4.86 pg / mL and ≥ 4.87 pg / mL) of the distribution ofcirculating levels of this cytokine, compared with those in lowest tertile (<3.43 pg / mL) showed significant increase in serum concentrations likely to have decreased HDL-c. This study contributes to better understanding of associations between markers of interest (TNF-α and IL-6) and the risk factors for the occurrence of diseases associated with MS. Moreover, this study revealed the association of mRNA expression of some inflammatory markers in PBMC with important variables in the surrounding context of metabolic diseases, even in healthy adults.
Several chronic diseases are accompanied by inflammatory processes and evidence continues to accumulate on the clinical relevance of these laboratory predictors of pathophysiological events. In this context, the present study was to evaluate, in young and clinically healthy individuals, plasma concentrations of TNF- and IL-6 and the expression of genes related to inflammation (TNF-α, IL-6, ICAM1, IL1R1 and IL-18) and their possible association with risk factors for the development of metabolic syndrome (MS). 161 individuals were evaluated about the anthropometry, body composition, dietary intake, and biochemical and clinical datas. The plasma level of TNF-α and IL-6 was conducted by immunoassay (ELISA) in EDTA plasma. Gene expression (GE) was performed on periferial blood mononuclear cells (PBMC) using real time PCR. Comparisons between groups were performed by the Mann-Whitney-U or Student-t in accordance with the distribution of variables. We used Spearman correlation, the linear regression model and the logistic regression. The results were presented as mean ± SD, interval of 95% and significance level of P <0.05. The results showed that plasma concentrations of TNF-α and IL-6 were higher in males (P <0.001), contrary to the values of GE was not different between genders. Individuals with higher circulating levels of TNF-α also showed higher body weight, waist circumference, waist/hip ratio, fat-free mass, systolic and diastolic blood pressure, glucose and uric acid levels, and on the other hand, smaller values of percentage of total fat, total cholesterol and HDL- and LDL-c (P <0.05). Individuals with higher circulating levels of IL-6 showed higher values of body weight, BMI, truncal fat, fat-free mass, systolic and diastolic blood pressure, HDL-c and uric acid, on the other hand, lower values of percentage of total fat, biceps and triceps skinfold, triglycerides, total cholesterol and LDL-c (P <0.05). The GE of this cytokine presented inverse concentrations of IL-6 in the plasm (P = 0.03). Individuals with higher TNF-α consumed more calories, protein, copper and fiber, but less iron in the diet (P<0.05). Those with higher IL-6 consumed more calories, macronutrients, fiber, iron and copper (P<0.05). By simple regression analysis, we found that the GE of ICAM1, the R1IL- 1 and IL-18 had a positive predictive effect on circulating levels of TNF-α (P<0.05 ). As for IL-6, body weight, fat-free mass, truncal adiposity, the systolic and diastolic blood pressure, levels of uric acid, glucose and LDL-c had a positive predictive effect, unlike percentage of total fat, circulating levels of total cholesterol and LDL-c and HDL-c, besides the concentration of selenium in nails, which had a negative predictive effect. Individuals who are positioned in the two last tertiles (3.48 to 5.08 pg / mL and ≥ 5.9 pg / mL) of the distribution of circulating levels of TNF-α, compared with those in the lowest tertile (<3.48 pg/mL) showed a significant increase the chances of having abdominal obesity (P <0.05). In the same way, those who werw in the last tertile, compared with those in smaller, showed a significant increase in the chances of having low levels of HDL-c. When the same analysis was performed for IL-6, it was found that individuals who were in the two largest tertiles (3.43 to 4.86 pg / mL and ≥ 4.87 pg / mL) of the distribution ofcirculating levels of this cytokine, compared with those in lowest tertile (<3.43 pg / mL) showed significant increase in serum concentrations likely to have decreased HDL-c. This study contributes to better understanding of associations between markers of interest (TNF-α and IL-6) and the risk factors for the occurrence of diseases associated with MS. Moreover, this study revealed the association of mRNA expression of some inflammatory markers in PBMC with important variables in the surrounding context of metabolic diseases, even in healthy adults.
Descrição
Palavras-chave
Biomarcadores inflamatórios, TNF-α, IL-6, Síndrome metabólica, Inflammatory biomarkers, TNF-α, IL-6, Metabolic syndrome
Citação
ROCHA, José Luiz Marques. Inflammatory biomarkers and metabolic syndrome in healthy young adults. 2012. 154 f. Dissertação (Mestrado em Valor nutricional de alimentos e de dietas; Nutrição nas enfermidades agudas e crônicas não transmis) - Universidade Federal de Viçosa, Viçosa, 2012.