Food intake in early life and epigenetic modifications of pro-opiomelanocortin expression in arcuate nucleus.

The prevalence of obesity is increasing in nowadays societies and, despite being a multifactorial disease, it has a significant correlation with food intake. The control of food intake is performed by neurons of the arcuate nucleus of the hypothalamus (ARC), which secret orexigenic and anorexigenic neuropeptides, such as proopiomelanocortin (POMC), under stimulation of, e.g., ghrelin, insulin, and leptin. Insulin, uses inositol 1,4,5-trisphosphate/serine-threonine kinase (IP3/Akt) pathways and stimulates the exclusion of (Forkhead box protein O1) FOXO1 from the nucleus and thereby does the inactivation of the inhibition of POMC expression, while Leptin stimulates signal transducer and activator of transcription 3 (STAT3) phosphorylation and POMC expression. Epigenetic modifications of the synthesis of these neuropeptides can lead to an increased caloric intake, which, in turn, is an important risk factor for obesity and its comorbidities. Epigenetic modifications are reversible, so the search for epigenetic targets has significant scientific and therapeutic appeal. In this review, we synthesize the effect of food intake on the epigenetic modifications of Neuropeptide Y and Pro-opiomelanocortin of ARC and its relationships with obesity development and comorbidities. We found that there is no consensus on the methylation of neuropeptides when the evaluations are carried out in different promoters. Based on reports carried on in the early life in laboratory animals, which is the timeline that the vast majority of author used to study this topic, chronic inflammation, defects in insulin and leptin signaling may be linked to changes occurring in the phosphoinositide 3-kinase/Akt (PI3K/Akt) and/or STAT3/SOCS3 (cytokine signaling 3) pathways. In its turn, the epigenetic modifications related to increased food intake and reduced energy expenditure may be associated with PI3K/Akt and STAT3/SOCS3 signaling disruption and Pro-opiomelanocortin expression.

Transcription of mtDNA and dyslipidemia are ameliorated by aerobic exercise in type 2 diabetes.

Physical inactivity and unhealthy food intake are strongly associated with the growing prevalence of type 2 diabetes (T2D). Dyslipidemia, a characteristic of T2D patient, contributes to an increase in intra-myocellular lipid accumulation and mitochondria dysfunction, in skeletal muscle cells and further to insulin resistance. The aim of this study was to evaluate the effect of aerobic exercise on dyslipidemia, mitochondrial homeostasis and mitochondrial DNA (mtDNA) transcription in T2D- induced animals. Wistar rats (8 weeks old) were fed a diet containing 60% fat over 9 weeks, at day 14 a single injection of STZ (25 mg/kg) was administered (T2D-induced). At week 3 of the experiment half of the animals started on an aerobic exercise 5-days/week. Blood and soleus muscle were collected at 9th experimental week. Abdominal fat, blood glucose, triglyceride, low-density-lipoprotein and high-density lipoprotein (HDL), and cellular mtDNA copy number, cytochrome b (cytb) mRNA and 8-isoprostane were measured. T2D-induced animals exhibited changes in blood glucose, weight gain, abdominal fat, LDL and muscular 8-isoprostane, mtDNA copy number and cytb mRNA. Aerobic exercise attenuated the increase in weight gain and abdominal fat and the decreased cytb mRNA, and increased HDL. Our results suggest that aerobic exercise might not affect all characteristics related to the development of T2D in the same way. However, since T2D is a multifactorial disease, improvement in parameters such as HDL levels, abdominal fat and weight gain induced by aerobic exercise might delay or inhibit the onset of T2D.

The role of mitochondrial DNA damage at skeletal muscle oxidative stress on the development of type 2 diabetes.

Reduced cellular response to insulin in skeletal muscle is one of the major components of the development of type 2 diabetes (T2D). Mitochondrial dysfunction involves in the accumulation of toxic reactive oxygen species (ROS) that leads to insulin resistance. The aim of this study was to verify the involvement of mitochondrial DNA damage at ROS generation in skeletal muscle during development of T2D. Wistar rats were fed a diet containing 60% fat over 8 weeks and at day 14 a single injection of STZ (25 mg/kg) was administered (T2D-induced). Control rats received standard food and an injection of citrate buffer. Blood and soleus muscle were collected. Abdominal fat was quantified as well as glucose, triglyceride, LDL, HDL, and total cholesterol in plasma and mtDNA copy number, cytochrome b (cytb) mRNA, 8-hydroxyguanosine, and 8-isoprostane (a marker of ROS) in soleus muscle. T2D-induced animal presented similar characteristics to humans that develop T2D such as changes in blood glucose, abdominal fat, LDL, HDL and cholesterol total. In soleus muscle 8-isoprostane, mtDNA copy number and 8-hydroxyguanosine were increased, while cytb mRNA was decreased in T2D. Our results suggest that in the development of T2D, when risks factors of T2D are present, intracellular oxidative stress increases in skeletal muscle and is associated with a decrease in cytb transcription. To overcome this process mtDNA increased but due to the proximity of ROS generation, mtDNA remains damaged by oxidation leading to an increase in ROS in a vicious cycle accounting to the development of insulin resistance and further T2D.

The link between hypothalamic epigenetic modifications and long-term feeding control.

The incidence of obesity, one of the main risks for type 2 diabetes and cardiovascular disease, has been rising, and changes in eating behavior are associated with this increasing rate. Body weight is maintained via a complex integration of endocrine and neuronal inputs that regulate the control of orexigenic and anorexigenic neuropeptides in the arcuate nucleus of the hypothalamus. Overfeeding may disrupt the mechanisms of feeding control, increasing orexigenic peptides such as neuropeptide Y (NPY), and/or decreasing the anorexigenic peptide proopiomelanocortin (POMC) leading to a change in energy balance and body-weight index. Despite of the great interest in this field, the mechanism by which expression of POMC and NPY is modified is not entirely clear. Over the past decades, studies have demonstrated that epigenetic modifications such as DNA methylation, histone modification and changes in miRNA dynamics, could be modulated by external stimuli and these could affect protein expression in different cells. Therefore, this review discusses the recent reports that link epigenetic modifications in the hypothalamus to changes on long-term feeding control and its role in the onset of obesity.

Moderate physical exercise attenuates the alterations of feeding behaviour induced by social stress in female rats.

Epidemiological studies have demonstrated that stress-related disorders, such as the increase on the caloric intake, are twice as common in women as in men, but surprisingly, very few studies have been tested this subject on female experimental animals. Additionally, it has been proposed that regular physical exercise can improve the deleterious effects of stress. Therefore, the present longitudinal study, performed in female rats, aimed to test the influence of chronic stress (ST) imposed by social isolation on the animals' caloric intake and to assess the effect of regular physical exercise of low intensity on this behaviour. In 4 groups of Wistars rats (control sedentary, n = 6; control exercised, n = 6; ST sedentary, n = 6; ST exercised, n = 6), body weight, food intake, abdominal fat weight, adrenal weight, corticosterone metabolites in faeces and plasma insulin levels were measured during the experimental protocol and/or at its end. The results showed that social isolation was not able to modify the amount of abdominal fat and the body weight; however, it promoted significant increases in the corticosterone metabolites and in the amount of caloric intake, which were attenuated in exercised rats. Additionally, exercised groups presented lower levels of fasting insulin than sedentary groups. Therefore, the present study demonstrated that regular physical exercise of low intensity attenuates the corticosterone metabolites and overeating behaviour triggered by social stress.

The effect of physical exercise on orexigenic and anorexigenic peptides and its role on long-term feeding control.

Over the past decades, life-styles changing have led to exacerbated food and caloric intake and a reduction in energy expenditure. Obesity, main outcome of these changes, increases the risk for developing type 2 diabetes, cardiovascular disease and metabolic syndrome, the leading cause of death in adult and middle age population. Body weight and energy homeostasis are maintained via complex interactions between orexigenic and anorexigenic neuropeptides that take place predominantly in the hypothalamus. Overeating may disrupt the mechanisms of feeding control, by decreasing the expression of proopiomelanocortin (POMC) and α-melanocyte stimulating hormone (α-MSH) and increasing orexigenic neuropeptide Y (NPY) and agouti-related peptide (AgRP), which leads to a disturbance in appetite control and energy balance. Studies have shown that regular physical exercise might decrease body-weight, food intake and improve the metabolic profile, however until the currently there is no consensus about its effects on the expression of orexigenic/anorexigenic neuropeptides expression. Therefore, we propose that the type and length of physical exercise affect POMC/αMSH and NPY/AgRP systems differently and plays an important role in feeding behavior. Moreover, based on the present reports, we hypothesize that increased POMC/αMSH overcome NPY/AgRP expression decreasing food intake in long term physical exercise and that results in amelioration of several conditions related to overweight and obesity.

The effect of exercise on skeletal muscle glucose uptake in type 2 diabetes: An epigenetic perspective.

Changes in eating habits and sedentary lifestyle are main contributors to type 2 diabetes (T2D) development, and studies suggest that epigenetic modifications are involved with the growing incidence of this disease. Regular exercise modulates many intracellular pathways improving insulin resistance and glucose uptake in skeletal muscle, both early abnormalities of T2D. Mitochondria dysfunction and decreased expression of glucose transporter (GLUT4) were identified as main factors of insulin resistance. Moreover, it has been suggested that skeletal muscle of T2D subjects have a different pattern of epigenetic marks on the promoter of GLUT4 and PGC1, main regulator of mitochondrial function, compared with nondiabetic individuals. Recent studies have proposed that regular exercise could improve glucose uptake by the attenuation of such epigenetic modification induced at GLUT4, PGC1 and its downstream regulators; however, the exact mechanism is still to be understood. Herein we review the known epigenetic modifications on GLUT4 and mitochondrial proteins that lead to impairment of skeletal muscle glucose uptake and T2D development, and the effect of physical exercise at these modifications.

Knowledge among physical education professionals about poliomyelitis and post-poliomyelitis syndrome: a cross-sectional study in Brazil.

BACKGROUND: Post-poliomyelitis syndrome is a clinical condition that can affect poliomyelitis survivors with the onset of new symptoms several years after the acute disease. These symptoms include new muscular weakness, fatigue, pain, onset or aggravation of muscle atrophy, muscle cramps, onset or aggravation of pre-existing difficulties in accomplishing daily life activities, cold intolerance, sleep disorders, dysphonia or dysphagia, and respiratory deficiency. The treatment of post-poliomyelitis syndrome requires a multiprofessional health team because the rehabilitation procedures include lifestyle changes, physiotherapy, avoidance of secondary complications, and physical exercise. As physical exercise is prescribed by physical education professionals, the assessment of knowledge about post-poliomyelitis syndrome among these professionals is very relevant. The aim of this study was to evaluate poliomyelitis and post-poliomyelitis syndrome knowledge among physical education professionals in Brazil. METHODS: We invited participants with an academic degree in physical education (n = 217) to participate in this study. A self-administered survey (30 questions) was designed to probe knowledge about poliomyelitis and post-poliomyelitis syndrome. From the survey, we created a questionnaire to evaluate the performance of the professionals. The questionnaire was composed of 20 questions and a score was provided, varying from 0 (totally uninformed) to 20 (well informed). RESULTS: Approximately 73% of surveyed participants had never heard of post-poliomyelitis syndrome, and only 19.4% had received information about the disease. Among those surveyed, 61.8% did not know whether restriction of physical activities was warranted for people with poliomyelitis sequelae, and only 32.3% knew that physical exercise (especially intense exercise) should be limited for patients with sequelae of paralytic poliomyelitis. CONCLUSION: The findings of the present study indicate a critical need for improvement of knowledge about post-poliomyelitis syndrome among Brazilian physical education professionals.

Association between blood pressure, body mass index, eating habits, and physical activity in adolescents / Associação entre pressão arterial, índice de massa corporal, hábitos alimentares e atividade física em adolescentes

AIMS: This study sought to analyze blood pressure and its association with eating behavior, physical activity, and body mass index in high school students. METHODS: A cross-sectional study was performed with high school students from midwestern Brazil. Blood pressure was measured according to the guidelines outlined by the Brazilian Society of Cardiology. Nutritional status was assessed in accordance with the Brazilian Food and Nutrition Surveillance System (Sistema de Vigilância Alimentar Nutricional, SISVAN), according to the standard reference of the National Health and Nutritional Examination Survey (NHANES II), and the level of physical activity was assessed by the International Physical Activity Questionnaire-Short Form. The chi-square test and the Mann-Whitney U test were used for characterization of the population and comparisons between genders and normotensive and prehypertensive subjects. Bivariate and multivariate regression analyses were performed to verify the relationship between blood pressure, physical activity, and eating behavior. The significance level was set at p<0.05. RESULTS: Prehypertension was detected in 26% of the students and overweight frequency was higher than the national average (38% for girls and 20% for boys). Concerning eating behavior, students' nutritional habits were "very good" in 7%, "regular" in 68%, and "poor" in 24%. In bivariate analyses, systolic blood pressure and blood pressure percentile were positively associated with body mass index. In multivariate analyses, there were positive associations between eating behavior and body mass index with diastolic blood pressure: when body mass index was high and the eating behavior score was low (unhealthy eating habits), diastolic blood pressure was high. No relationship was observed between blood pressure and physical activity. CONCLUSIONS: The adolescents assessed in this study showed a high frequency of prehypertension. Body mass index was positively associated with high blood pressure, indicating that a high body mass index is a risk factor for the development of hypertension among adolescents. Therefore, early intervention to control body mass index may be a valuable strategy to prevent overweight, obesity, and hypertension.

OBJETIVOS: Este estudo procurou analisar a pressão arterial e suas associações com comportamento alimentar, atividade física e índice de massa corporal em estudantes do ensino médio. MÉTODOS: Um estudo transversal foi conduzido com estudantes do ensino médio do Centro-Oeste do Brasil. A pressão arterial foi mensurada de acordo com as diretrizes da Sociedade Brasileira de Cardiologia. O estado nutricional foi classificado de acordo com o Sistema de Vigilância Alimentar Nutricional (SISVAN), com base nos critérios de referência do National Health and Nutritional Examination Survey (NHANES II); e o nível de atividade física foi avaliado por meio do Questionário Internacional de Atividade Física, Forma Curta. O teste do Qui quadrado e o teste de Mann-Whitney foram usados para as comparações entre os gêneros e os sujeitos com pressão arterial normal e pré-hipertensão. As associações entre pressão arterial, atividade física e comportamento alimentar foram avaliadas pelos testes de regressão bivariada e multivariada. O nível de significância estabelecido foi de p<0,05. RESULTADOS: Foi detectada pré-hipertensão em 26% dos estudantes e a frequência de sobrepeso foi maior do que a média nacional, 38% em meninas e 20% em meninos. Em relação ao comportamento alimentar, foram encontrados 7% de estudantes com hábitos "muito bons", 68% "regulares" e 24% com hábitos nutricionais "ruins". Nas análises bivariadas, a pressão arterial sistólica e o percentil da pressão arterial associaram-se positivamente com índice de massa corporal. Nas análises multivariadas houve associação positiva entre comportamento alimentar e índice de massa corporal com pressão arterial diastólica: quando o índice de massa corporal era alto e o escore nutricional era baixo (hábitos alimentares não saudáveis), a pressão arterial diastólica era alta. Não foi observada relação entre pressão arterial e nível de atividade física. CONCLUSÕES: Os adolescentes incluídos no estudo apresentaram alta frequência de pré-hipertensão. O índice de massa corporal associouse positivamente com pressão arterial, de forma que o índice de massa corporal elevado pode ser considerado como fator de risco para o desenvolvimento de hipertensão arterial em adolescentes. Assim, a intervenção precoce para controlar o índice da massa corporal pode ser uma estratégia valiosa para prevenir o sobrepeso, a obesidade e a hipertensão arterial.

Abordagem multiprofissional no cuidado à saúde de pacientes do programa HiPErDiA / Multiprofessional approach to health care in patients of the HIPERDIA program

A Hipertensão Arterial Sistêmica (HAS) é uma doença crônica e fator de risco para o desenvolvimento de doenças cardiovasculares, cerebrovasculares e doenças renais crônicas, que podem levar a morte, sendo um grave problema de saúde pública. O principal fator apontado para a falta de sucesso no controle da HAS e prevenção das comorbidades é a não adesão ao tratamento, relacionando-se com a frequência de comparecimento às consultas, uso correto da medicação (tratamento farmacológico) e alterações comportamentais, que determinam o sucesso do tratamento não farmacológico (controle alimentar e prática de exercício físico). Objetivou-se avaliar nos pacientes do programa HIPERDIA a adesão ao tratamento e os fatores de risco relacionados à hipertensão arterial. Foram analisados os prontuários de 561 pacientes entre os anos de 1998 e 2010. A adesão foi avaliada pela frequência dos pacientes às consultas e pela prevalência dos fatores de risco, antes e após a intervenção. A evolução do quadro clínico foi analisada durante 12 anos, com a condição de inclusão de comparecimento a 2 consultas anuais. Observou-se baixa frequência de comparecimento às consultas, pois dos 561 pacientes iniciais, somente 110 satisfizeram à condição do estudo. Os fatores de risco prevalentes no início e no fimdo estudo foram sedentarismo, obesidade e dieta alimentar desequilibrada, demonstrando baixa adesão ao tratamento não farmacológico. Todavia, entre os pacientes que permaneceram no programa, houve controle eficiente da pressão arterial, indicando a importância da assistência institucionalizada

High Blood Pressure (HBP) is a chronic disease and a risk factor for cardiovascular, cerebrovascular and chronic kidney disease, which can lead to death. In addition, it is a serious public health problem. The main factor for the lack of success in controlling HBP and prevention of comorbidities is the non-compliance to treatment, which is related to the frequency of attendance to medical appointments, proper use of medication (drug treatment), and behavioral changes that determine the success of non-pharmacological treatment (diet control and physical exercise). The objective of the present study was to evaluate the risk factors related to hypertension and patient compliance to the HIPERDIA program. The medical records of 561 patients were analyzed from 1998 to 2010. The compliance to the treatment was assessed by the frequency of ambulatory visits, while the prevalence of risk was evaluated before and after the intervention. The progression of the disease was analyzed for 12 years, with the condition to include attendance at 2 annual consultations. It was observed low frequency of consultations, since only 110 patients from the 561 initially recruited complied with the condition of the study. The risk factors prevalent atthe beginning and in the end of the study were sedentary life style, obesity and unbalanced diet, demonstrating poor adherence to non-pharmacological treatment. However, among patients who remained in the program, there was effective blood pressure control, indicating the importance of institutionalized care.