RESUMO
Noonan syndrome (NS) and NS related disorders (NRD) are frequent monogenic diseases. Pathogenic variants in PTPN11 are observed in approximately 50% of these NS patients. Several pleiotropic phenotypes have previously been described in this condition. This study aimed at characterizing glucose and lipid profiles in patients with NS/NRD. We assessed fasting blood glucose, insulin, cholesterol (total and fractions), and triglyceride (TG) levels in 112 prepubertal children and 73 adults. Additionally, an oral glucose tolerance test (OGTT) was performed in 40 children and 54 adults. Data were analyzed between age groups according to the presence (+) or absence (-) of PTPN11 mutation. Prepubertal patients with NS/NRD were also compared with a control group. Despite the lean phenotype of children with NS/NRD, they presented an increased frequency of low HDL-cholesterol (63% in PTPN11+, 59% in PTPN11- and 16% in control, p < .001) and high TG levels (29% in PTPN11+, 18% in PTPN11- and 2.3% in control). PTPN11+ patients had a higher median HOMA-IR (1.0, ranged from 0.3 to 3.2) in comparison with PTPN11- (0.6; 0.2 to 4.4) and controls (0.6; 0.4 to 1.4, p = .027). Impaired glucose tolerance was observed in 19% (10:54) of lean adults with NS/NRD assessed by OGTT. Moreover, women with PTPN11 mutations had lower HDL-cholesterol levels than those without. Our results suggest that children and young adult patients with NS/NRD have an unfavorable metabolic profile characterized by low HDL, a tendency of elevated TGs, and glucose metabolism impairment despite a lean phenotype.
Assuntos
Metaboloma , Síndrome de Noonan/patologia , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , Seguimentos , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Síndrome de Noonan/genética , Síndrome de Noonan/metabolismo , Fenótipo , Prognóstico , Adulto JovemRESUMO
BACKGROUND: The insertion/deletion polymorphism in the gene encoding the angiotensin-converting enzyme (ACE I/D) was associated with arterial hypertension and obesity in adults, but the data in children are scarce and yielded contrasting results. We assessed the impact of the ACE I/D on blood pressure and obesity related traits in a Brazilian cohort of obese children and adolescents. METHODS AND RESULTS: ACE I/D was genotyped in 320 obese children and adolescents (64% of girls) aged 7-16years, referred for a weight-loss program. We observed an association of the D-allele with blood pressure and with pre-hypertension/hypertension in boys (odds ratio 2.44, 95% C.I. 1.34-4.68, p=0.005 for a codominant model). The D-allele, insulin resistance and body fat mass had independent and additive effects and explained 14% of the variance of pre-hypertension/hypertension. The BMI, waist circumference, and body fat mass were significantly higher in DD/ID boys than in II boys (p<0.005). Allelic associations with obesity related traits were independent of the association with blood pressure. No genotype associations were observed in girls. CONCLUSIONS: The D-allele of the ACE I/D polymorphism was associated with arterial hypertension and with obesity related traits in boys, but not in girls, in a cohort of obese children and adolescents. These associations were independent of each other, as well as of the effects of other confounding traits such as insulin secretion, insulin sensitivity and glucose tolerance. Our results are in agreement with experimental evidences suggesting that the renin-angiotensin system plays a role in the regulation of visceral adipose tissue accumulation.
Assuntos
Adiposidade/genética , Hipertensão/genética , Mutação INDEL , Obesidade/genética , Peptidil Dipeptidase A/genética , Adolescente , Pressão Arterial/genética , Criança , Estudos de Coortes , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Hipertensão/enzimologia , Gordura Intra-Abdominal/enzimologia , Gordura Intra-Abdominal/patologia , Masculino , Obesidade/enzimologia , Obesidade/fisiopatologia , Polimorfismo GenéticoRESUMO
Body weight excess has an increasingly high prevalence in the world. Obesity is a complex disease of multifactorial origin with a polygenic condition affected by environmental factors. Weight loss is a primary strategy to treat obesity and its morbidities. Weight changes through life depend on the interaction of environmental, behavioral and genetic factors. Interindividual variation of weight loss in response to different types of interventions (behavioral, caloric restriction, exercise, drug or surgery) has been observed. In this article, currently available data on the role of candidate gene polymorphisms in weight loss are reviewed. Even though control of weight loss by genotype was described in twin and family studies, it is premature to recommend use of genotyping in the design of therapeutic diets or drug treatment. Future studies will have to be large in order to assess the effects of multiple polymorphisms, and will have to control factors other than diet.
Assuntos
Peso Corporal/genética , Obesidade/terapia , Polimorfismo Genético , Redução de Peso/genética , Regulação do Apetite/genética , Distribuição da Gordura Corporal , Dieta , Metabolismo Energético , Exercício Físico , Variação Genética , Genótipo , Humanos , Metabolismo dos Lipídeos/genética , Obesidade/genéticaRESUMO
Body weight excess has an increasingly high prevalence in the world. Obesity is a complex disease of multifactorial origin with a polygenic condition affected by environmental factors. Weight loss is a primary strategy to treat obesity and its morbidities. Weight changes through life depend on the interaction of environmental, behavioral and genetic factors. Interindividual variation of weight loss in response to different types of interventions (behavioral, caloric restriction, exercise, drug or surgery) has been observed. In this article, currently available data on the role of candidate gene polymorphisms in weight loss are reviewed. Even though control of weight loss by genotype was described in twin and family studies, it is premature to recommend use of genotyping in the design of therapeutic diets or drug treatment. Future studies will have to be large in order to assess the effects of multiple polymorphisms, and will have to control factors other than diet.
A prevalência do excesso de peso cresce no mundo todo. De origem multifatorial, a obesidade é uma doença complexa, com condição poligênica afetada por fatores ambientais. A perda de peso é a estratégia primária utilizada para prevenir e tratar a obesidade bem como suas comorbidades. Mudanças de peso durante a vida dependem da interação entre fatores ambientais, comportamentais e genéticos. Observa-se grande variação da perda de peso entre indivíduos em resposta a diferentes modelos de intervenções (comportamentais, restrições da ingesta cálorica, exercícios físicos, drogas antiobesidade ou cirurgias). Este artigo é uma revisão atual da literatura disponível, que busca abordar o papel dos polimorfismos dos genes candidatos à obesidade e sua influência na perda de peso. Apesar da interação do genótipo na perda de peso corporal, descrita nos estudos de gêmeos e familiares, é prematuro recomendar o uso da genotipagem para estratégias de perda de peso. É necessário ampliar as pesquisas sobre os efeitos sinérgicos dos polimorfismos genéticos com coorte maior e associá-los não somente à restrição alimentar mas também às outras intervenções que auxiliam na perda de peso.
Assuntos
Humanos , Peso Corporal/genética , Obesidade/terapia , Polimorfismo Genético , Redução de Peso/genética , Regulação do Apetite/genética , Distribuição da Gordura Corporal , Dieta , Metabolismo Energético , Exercício Físico , Variação Genética , Genótipo , Metabolismo dos Lipídeos/genética , Obesidade/genéticaRESUMO
This study examined forearm vasodilatation during mental challenge and exercise in 72 obese children (OC; age = 10 +/- 0.1 years) homozygous with polymorphism in the allele 27 of the beta-2-adrenoceptors: Gln27 (n = 61) and Glu27 (n = 11). Forearm blood flow was recorded during 3 min of each using the Stroop color-word test (MS) and handgrip isometric exercise. Baseline hemodynamic and vascular measurements were similar. During the MS, peak forearm vascular conductance was significantly greater in group Glu27 (Delta = 0.35 +/- 0.4 vs. 0.12 +/- 0.1 units, respectively, p = .042). Similar results were found during exercise (Delta = 0.64 +/- 0.1 vs. 0.13 +/- 0.1 units, respectively, p = .035). Glu27 OC increased muscle vasodilatory responsiveness upon the MS and exercise.
Assuntos
Cognição , Exercício Físico , Músculo Esquelético/metabolismo , Obesidade/metabolismo , Polimorfismo Genético , Receptores Adrenérgicos beta 2/genética , Vasodilatação , Antropometria , Índice de Massa Corporal , Criança , Proteção da Criança , Teste de Esforço , Feminino , Antebraço/irrigação sanguínea , Força da Mão , Hemodinâmica , Humanos , Masculino , Obesidade/fisiopatologia , Psicometria , Receptores Adrenérgicos beta 2/metabolismo , Estresse PsicológicoRESUMO
This study aimed to determine the occurrence of symptoms of binge eating (BE) among children and adolescents seeking treatment for their obesity, as well as to evaluate their diet composition and metabolic characteristics. The Binge Eating Scale (BES) was answered by 128 children and adolescents (10.77+/-2.04 years, BMI 29.15+/-4.98 kg/m2, BMI Z score 2.28+/-0.46, 53.91% pubescent), who were classified into two subgroups--binge eaters (score greater than or equal to 18 points) and non-binge eaters (score lower than 18 points). Anthropometric data, body composition and Tanner stages were collected and dietary evaluation conducted. Blood pressure was determined, and glucose, lipid profile and insulin assays were performed. Insulin resistance was determined using HOMA-IR. BE symptoms were present in 39.06% of patients. Carbohydrate intake in diet composition was significantly higher among binge eaters. Children with BE did not demonstrate significant dissimilar metabolic characteristics when compared to their counterparts without BE. Therefore, BE seems to be a prevalent problem among children and adolescents seeking help for their obesity. When associated with obesity, this eating behaviour can influence macronutrient consumption through increased carbohydrate intake. Further research would be valuable to verify the reproducibility of these findings.
Assuntos
Bulimia/epidemiologia , Fenômenos Fisiológicos da Nutrição Infantil/fisiologia , Dieta , Carboidratos da Dieta/administração & dosagem , Obesidade/metabolismo , Obesidade/psicologia , Antropometria , Composição Corporal , Índice de Massa Corporal , Estudos de Casos e Controles , Criança , Carboidratos da Dieta/metabolismo , Feminino , Humanos , Masculino , Inquéritos e QuestionáriosRESUMO
AIM: A cross-sectional study was conducted to explore osteoarticular alterations in obese children. METHODS: Twenty-five boys and 24 girls (mean age: 10.8+/-2.07 years) with a body mass index (BMI) above the 95th percentile were compared with 28 boys and 19 girls (controls, mean age: 10.4+/-2.3 years) with a BMI below the 80th percentile. RESULTS: A higher frequency of at least one osteoarticular manifestation was observed in obese patients (55%) compared with the control group (23%) (P=0.001). A statistically significant association was also found between obesity and lower back pain, genu valgum, genu recurvatum and tight quadriceps. Fibromyalgia tender points (=11) were present at similar frequency in both groups (obese: 3/38 (9%) vs. control: 1/48 (2%)). CONCLUSION: The present data suggest that obesity has a negative impact on osteoarticular health by promoting biomechanical changes in the lumbar spine and lower extremities.
Assuntos
Artralgia/etiologia , Dor Lombar/etiologia , Obesidade/complicações , Índice de Massa Corporal , Estudos de Casos e Controles , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Obesidade/fisiopatologiaRESUMO
OBJECTIVE: The purpose of this study was to analyze growth hormone (GH) concentrations in obese women before and after Roux-en-Y gastric bypass (RYGBP) and how resulting changes in weight, fat mass, ghrelin levels, and insulin sensitivity affect GH secretion. RESEARCH METHODS AND PROCEDURES: Blood was sampled at 20-minute intervals for 24 hours in 10 non-diabetic premenopausal severely obese women before and 6 months after RYGBP. GH concentrations were measured in all samples, and serum ghrelin was collected at five time-points. RESULTS: After a 27% BMI drop (55.9 +/- 6.2 to 40.7 +/- 5.8 kg/m2), blunted GH profiles underwent partial recovery. Basal, postprandial, and mean ghrelin concentrations were not changed. A negative correlation was found between mean GH levels and insulin and homeostasis model assessment (p < 0.01). BMI accounted for 54% of GH variation. DISCUSSION: Partial recovery of GH secretion after RYGBP-induced weight loss suggests that a blunted secretion is not a causal factor of obesity but a consequence of the obese state and does not seem to be ghrelin-level dependent.
Assuntos
Derivação Gástrica , Hormônio do Crescimento/metabolismo , Obesidade/sangue , Obesidade/cirurgia , Hormônios Peptídicos/metabolismo , Adulto , Composição Corporal , Peso Corporal/fisiologia , Feminino , Grelina , Hormônio do Crescimento/sangue , Humanos , Resistência à Insulina/fisiologia , Estudos Longitudinais , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Hormônios Peptídicos/sangue , Período Pós-Prandial/fisiologia , Estudos ProspectivosRESUMO
BACKGROUND: The effects of diet and diet plus exercise training on muscle vasodilatation during physiological maneuvers in obese children are unknown. We tested the hypothesis that (1) blood pressure (BP) and forearm vascular conductance (FVC) responses during handgrip exercise and mental stress would be altered in obese children and (2) diet plus exercise training would restore BP and FVC responses during exercise and mental stress in obese children. METHODS AND RESULTS: Thirty-nine obese children (aged 10+/-0.2 years) were randomly divided into 2 groups: diet plus exercise training (n=21; body mass index [BMI]=28+/-0.5 kg/m2) and diet (n=18; BMI=30+/-0.4 kg/m2). Ten age-matched lean control children (BMI=17+/-0.5 kg/m2) were also studied. Forearm blood flow was measured by venous occlusion plethysmography. BP was monitored noninvasively. Handgrip exercise was performed at 30% maximal voluntary contraction for 3 minutes. Stroop color word test was performed for 4 minutes. Baseline BP was significantly higher and FVC was significantly lower in obese children. During exercise and mental stress, BP responses were significantly higher and FVC responses were significantly lower in obese children. Diet and diet plus exercise training significantly reduced body weight. Diet and diet plus exercise training significantly decreased BP levels during exercise and mental stress. Diet plus exercise training, in contrast to diet alone, significantly increased FVC responses during exercise (3.7+/-0.3 versus 5.6+/-0.4 U; P=0.01) and mental stress (3.5+/-0.5 versus 4.5+/-0.4 U; P=0.02). After diet plus exercise training, BP and FVC responses during exercise and mental stress were similar between obese children and the control group. CONCLUSIONS: Obesity exacerbates BP responses and impairs FVC responses during exercise and mental stress in children. Diet and exercise training restore BP and FVC responses in obese children.
Assuntos
Pressão Sanguínea , Dietoterapia , Terapia por Exercício , Obesidade/fisiopatologia , Obesidade/terapia , Vasodilatação , Índice de Massa Corporal , Peso Corporal , Criança , Feminino , Hemodinâmica , Humanos , Masculino , Músculo Esquelético/irrigação sanguínea , Consumo de Oxigênio , Fluxo Sanguíneo Regional , Estresse Psicológico/fisiopatologiaRESUMO
We hypothesized that the muscle vasodilatation during mental stress and exercise would vary among humans who are polymorphic at alleles 16 and 27 of the beta(2)-adrenoceptors. From 216 preselected volunteers, we studied 64 healthy, middle-aged normotensive women selected to represent three genotypes: homozygous for the alleles Arg(16) and Gln(27) (Arg(16)/Gln(27), n = 34), Gly(16) and Gln(27) (Gly(16)/Gln(27), n = 20), and Gly(16) and Glu(27) (Gly(16)/Glu(27), n = 10). Forearm blood flow (plethysmography) and muscle sympathetic nerve activity (microneurography) were recorded during 3-min Stroop color-word test and 3-min handgrip isometric exercise (30% maximal voluntary contraction). Baseline muscle sympathetic nerve activity, forearm vascular conductance, mean blood pressure, and heart rate were not different among groups. During mental stress, the peak forearm vascular conductance responses were greater in Gly(16)/Glu(27) group than in Gly(16)/Gln(27) and Arg(16)/Gln(27) groups (1.79 +/- 0.66 vs. 0.70 +/- 0.11 and 0.58 +/- 0.12 units, P = 0.03). Similar results were found during exercise (0.80 +/- 0.25 vs. 0.28 +/- 0.08 and 0.31 +/- 0.08 units, P = 0.02). Further analysis in a subset of subjects showed that brachial intra-arterial propranolol infusion abolished the difference in vasodilatory response between Gly(16)/Glu(27) (n = 6) and Arg(16)/Gln(27) (n = 7) groups during mental stress (0.33 +/- 0.20 vs. 0.46 +/- 0.21 units, P = 0.50) and exercise (0.08 +/- 0.06 vs. 0.03 +/- 0.03 units, P = 0.21). Plasma epinephrine concentration in Arg(16)/Gln(27) and Gly(16)/Glu(27) groups was similar. In conclusion, women who are homozygous for Gly(16)/Glu(27) of the beta(2)-adrenoceptors have augmented muscle vasodilatory responsiveness to mental stress and exercise.
Assuntos
Antebraço/irrigação sanguínea , Antebraço/fisiopatologia , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/fisiopatologia , Receptores Adrenérgicos beta 2/genética , Receptores Adrenérgicos beta 2/metabolismo , Estresse Psicológico/fisiopatologia , Velocidade do Fluxo Sanguíneo , Feminino , Glutamina/genética , Glutamina/metabolismo , Glicina/genética , Glicina/metabolismo , Força da Mão , Humanos , Mutação , Fenótipo , Esforço Físico , Relação Estrutura-Atividade , VasodilataçãoRESUMO
OBJECTIVE: We tested the hypothesis that muscle sympathetic nerve activity (MSNA) and forearm vascular resistance (FVR) would be augmented during mental stress or cold pressor test in healthy obese individuals compared with healthy lean individuals. RESEARCH METHODS AND PROCEDURES: Twenty-nine healthy obese women and 12 age-matched healthy lean women were involved in the study. MSNA was directly measured from the peroneal nerve using microneurography. Forearm blood flow was measured by venous occlusion plethysmography. Blood pressure (BP) was monitored noninvasively by an automatic BP cuff, and heart rate (HR) was measured by electrocardiogram. Stroop color word test was performed for 4 minutes, and the cold pressor test was performed for 2 minutes. RESULTS: Baseline MSNA and FVR were greater in the obese group than in the lean group. BP and HR were similar between groups. During mental stress, MSNA and FVR were greater in obese individuals than in lean individuals, although the magnitude of response was similar between groups. BP and HR similarly increased in obese and lean individuals. During the cold pressor test, MSNA, FVR, and BP were greater in obese individuals, but the magnitude of response was similar between groups. HR increased similarly during the cold pressor test in both obese and lean individuals. DISCUSSION: Obesity increases MSNA and FVR during mental stress and the cold pressor test. This inappropriate neurovascular control can be expected to have an adverse effect on the risk factors for cardiovascular events and, hence, should be considered in the treatment of obese patients.
Assuntos
Músculos/inervação , Obesidade/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Adulto , Pressão Sanguínea , Temperatura Baixa , Feminino , Antebraço/irrigação sanguínea , Frequência Cardíaca , Humanos , Imersão , Nervo Fibular/fisiopatologia , Pletismografia , Estresse Psicológico , Resistência VascularRESUMO
The mechanisms involved in the increase of orbital retro-ocular adipose tissue that occurs in Graves' ophthalmopathy (GO) are still unclear. In this condition, the orbital tissue shows glycosaminoglycans deposition produced by activated fibroblasts capable of undergoing adipocytic differentiation. Many genes are involved in adipogenic mechanisms including the transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-gamma). We evaluated the level of expression of the PPAR-gamma gene in normal and GO orbital adipose/connective tissue specimens using a quantitative and sensitive reverse transcription (RT) competitive polymerase chain reaction (PCR) assay. Our results show that the expression of PPAR-gamma was significantly greater in adipose/connective tissue from patients in the active stage of GO than in controls (150.8 +/- 103.9 and 24.0 +/- 4.9 amol/micro g of total RNA respectively, p < 0.05), while there was no significant difference between patients with inactive GO (58.8 +/- 40.6 aM/microg total RNA) and controls. These results suggest that increased PPAR-gamma gene expression in the active stage of GO may be dependent on the inflammatory process in this disease. We speculate that the increased orbital fat tissue observed in GO may be a consequence of the anti-inflammatory PPAR-gamma action.
Assuntos
Tecido Adiposo/metabolismo , Tecido Conjuntivo/metabolismo , Doença de Graves/metabolismo , Doença de Graves/patologia , Órbita/metabolismo , Receptores Citoplasmáticos e Nucleares/biossíntese , Fatores de Transcrição/biossíntese , Tecido Adiposo/crescimento & desenvolvimento , Tecido Adiposo/patologia , Adulto , Estudos de Casos e Controles , Feminino , Expressão Gênica , Doença de Graves/genética , Doença de Graves/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Órbita/crescimento & desenvolvimento , Órbita/patologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Receptores Citoplasmáticos e Nucleares/genética , Fatores de Transcrição/genéticaRESUMO
We studied the effects of a hypocaloric diet (D, n = 24, age: 32.2 +/- 1.4 yr, body mass index: 34.7 +/- 0.5 kg/m2) and a hypocaloric diet associated with exercise training (D + T, n = 25, age: 32.3 +/- 1.3 yr, body mass index: 32.9 +/- 0.4 kg/m2) on muscle metaboreflex control, muscle sympathetic nerve activity (MSNA, microneurography), blood pressure, and forearm blood flow (plethysmography) levels during handgrip exercise at 10% and 30% of maximal voluntary contraction in normotensive obese women. An additional 10 women matched by age and body mass index were studied as a nonadherent group. D or D + T significantly decreased body mass index. D or D + T significantly decreased resting MSNA (bursts/100 heartbeats). The absolute levels of MSNA were significantly lower throughout 10% and 30% exercise after D or D + T, although no change was found in the magnitude of response of MSNA. D + T, but not D, significantly increased resting forearm vascular conductance. D + T significantly increased the magnitude of the response of forearm vascular conductance during 30% exercise. D or D + T significantly increased MSNA levels during posthandgrip circulatory arrest when muscle metaboreflex is isolated. In conclusion, weight loss improves muscle metaboreflex control in obese women. Weight loss reduces MSNA, which seems to be centrally mediated. Weight loss by D + T increases forearm vascular conductance at rest and during exercise in obese individuals.