RESUMO
Abstract Objective: Obesity is a chronic disease caused by both environmental and genetic factors. Epidemiological studies have documented that increased energy intake and sedentary lifestyle, as well as a genetic contribution, are forces behind the obesity epidemic. Knowledge about the interaction between genetic and environmental components can facilitate the choice of the most effective and specific measures for the prevention of obesity. The aim of this study was to assess the association between the FTO, AKT1, and AKTIP genes and childhood obesity and insulin resistance. Methods: This was a case-control study in which SNPs in the FTO (rs99396096), AKT1, and AKTIP genes were genotyped in groups of controls and obese/overweight children. The study included 195 obese/overweight children and 153 control subjects. Results: As expected, the obese/overweight group subjects had higher body mass index, higher fasting glucose, HOMA-IR index, total cholesterol, low-density lipoprotein, and triglycerides. However, no significant differences were observed in genes polymorphisms genotype or allele frequencies. Conclusion: The present results suggest that AKT1, FTO, and AKTIP polymorphisms were not associated with obesity/overweight in Brazilians children. Future studies on the genetics of obesity in Brazilian children and their environment interactions are needed.
Resumo Objetivo A obesidade é uma doença crônica sustentada por fatores ambientais e genéticos. Estudos epidemiológicos documentaram que maior ingestão de energia e um estilo de vida sedentário, bem como a contribuição genética, são forças por trás da epidemia de obesidade. O conhecimento sobre a interação entre os componentes genéticos e ambientais pode facilitar a escolha das medidas mais efetivas e específicas para a prevenção da obesidade. O objetivo deste estudo foi avaliar a relação entre os genes associado à massa de gordura e à obesidade (FTO), homólogo 1 do oncogene viral v-akt de timoma murino (AKT1) e de ligação AKT1 (AKTIP) e a obesidade infantil e a resistência à insulina. Métodos Estudo de caso-controle no qual os polimorfismos de nucleotídeo simples (SNPs) nos genes FTO (rs99396096), AKT1 e AKTIP foram genotipados em grupos de controle e de crianças obesas/acima do peso. Foram recrutadas 195 crianças obesas/acima do peso e 153 indivíduos controle. Resultados Como esperado, os indivíduos do grupo obeso/acima do peso apresentaram maior índice de massa corporal, maior glicemia de jejum, índice do modelo de avaliação de homeostase (HOMA-IR), colesterol total, lipoproteína de baixa densidade e triglicerídeos. Contudo, não encontramos diferenças significativas no genótipo de polimorfismos gênicos ou nas frequências alélicas. Conclusão Nossos resultados sugerem que os polimorfismos AKT1, FTO e AKTIP não estavam associados à obesidade/sobrepeso em crianças brasileiras. São necessários estudos futuros sobre a genética da obesidade em crianças brasileiras e suas interações ambientais.
Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Proteínas Adaptadoras de Transdução de Sinal/genética , Sobrepeso/genética , Proteínas Reguladoras de Apoptose/genética , Obesidade Pediátrica/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Brasil/etnologia , Resistência à Insulina , Estudos de Casos e Controles , Polimorfismo de Nucleotídeo Único , Frequência do Gene/genéticaRESUMO
OBJECTIVE: Obesity is a chronic disease caused by both environmental and genetic factors. Epidemiological studies have documented that increased energy intake and sedentary lifestyle, as well as a genetic contribution, are forces behind the obesity epidemic. Knowledge about the interaction between genetic and environmental components can facilitate the choice of the most effective and specific measures for the prevention of obesity. The aim of this study was to assess the association between the FTO, AKT1, and AKTIP genes and childhood obesity and insulin resistance. METHODS: This was a case-control study in which SNPs in the FTO (rs99396096), AKT1, and AKTIP genes were genotyped in groups of controls and obese/overweight children. The study included 195 obese/overweight children and 153 control subjects. RESULTS: As expected, the obese/overweight group subjects had higher body mass index, higher fasting glucose, HOMA-IR index, total cholesterol, low-density lipoprotein, and triglycerides. However, no significant differences were observed in genes polymorphisms genotype or allele frequencies. CONCLUSION: The present results suggest that AKT1, FTO, and AKTIP polymorphisms were not associated with obesity/overweight in Brazilians children. Future studies on the genetics of obesity in Brazilian children and their environment interactions are needed.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Proteínas Reguladoras de Apoptose/genética , Sobrepeso/genética , Obesidade Pediátrica/genética , Proteínas Proto-Oncogênicas c-akt/genética , Adolescente , Brasil/etnologia , Estudos de Casos e Controles , Criança , Feminino , Frequência do Gene/genética , Humanos , Resistência à Insulina , Masculino , Polimorfismo de Nucleotídeo ÚnicoRESUMO
l-Arginine is substrate for nitric oxide (NO) synthesis and produces pulmonary vasodilatory effects in patients with pulmonary hypertension and in hypoxic animals. We hypothesized that l-arginine would attenuate the increase in oxidative stress and the pulmonary hypertension observed during acute pulmonary embolism (APE). Using an isolated lung perfusion rat model of APE, we examined whether l-arginine (0, 0.1, 0.5, 3, and 10 mmol/L) attenuates the pulmonary hypertension induced by the injection of 6.6 mg/kg of 300 microm Sephadex microspheres into the pulmonary artery. Thiobarbituric acid reactive species (TBA-RS) and nitrite/nitrate (NO(x)) concentrations were measured in lung perfusate to assess oxidative stress and NO production. l-Arginine (0.5, 3, and 10 mmol/L) attenuated (all P<0.05) APE-induced pulmonary hypertension by about 50%. The protective effect of l-arginine was completely reversed by inhibition of NO synthesis with l-NAME (4 mmol/L). In addition, l-arginine (0.5-10 mmol/L) blunted the increase in TBA-RS observed after APE. NO(x) tended to increase only when l-arginine (10 mmol/L) was added to the lung perfusate of non-embolized lungs. Taken together, these findings suggest that l-arginine attenuates APE-induced pulmonary hypertension through antioxidant mechanisms involving increased NO synthesis.
