The brain is the conductor: diet- induced inflammation overlapping physiological control of body mass and metabolism O cérebro é o maestro: inflamação induzida por dieta interfere no controle fisiológico da adiposidade corporal e do metabolismo

ABSTRACT Obesity is currently a worldwide pandemic. It affects more than 300 million humans and it will probably increase over the next 20 years. The consumption of calorie-rich foods is responsible for most of the obesity cases, but not all humans exposed to high-calorie diets develop the disease. This fact has prompted researchers to investigate the mechanisms linking the consumption of high-calorie diets to the generation of an imbalance between energy intake and expenditure. According to recent studies, the exposure to fat-rich diets induces an inflammatory response in the hypothalamic areas involved in the control of feeding and thermogenesis. The inflammatory process damages the neuronal circuitries that maintain the homeostatic control of the body's energy stores, therefore favoring body mass gain. This review will focus on the main advances obtained in this field. Arq Bras Endocrinol Metab. 2009;53(2):151-158. Keywords Inflammation; hypothalamus; metabolism; weight control; fat-rich diet RESUMO Obesidade é hoje um grave problema de saúde pública no mundo. Mais de 300 milhões de pessoas são obesas e esse número deve crescer substancialmente nos próximos 20 anos. As dietas ricas em calorias são a principal causa de obesidade, porém, nem todos os indivíduos expostos a dietas altamente calóricas se tornam obesos. Tal fato estimulou pesquisadores a investigarem os mecanismos que ligam o consumo de dietas ricas em calorias ao desenvolvimento de um balanço inadequado entre consumo e gasto energético. De acordo com estudos recentes, o consumo de dietas ricas em gorduras induz a ativação de uma resposta inflamatória nas áreas do hipotálamo envolvidas com o controle da fome e da termogênese. Tal processo inflamatório lesa os circuitos neuronais que mantêm o controle homeostático das reservas corporais de energia, favorecendo assim o ganho de massa adiposa. Esta revisão irá focar os principais avanços obtidos nesta área. Arq Bras Endocrinol Metab. 2009;53(2):151-158. Descritore

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Lipid Overload During Gestation And Lactation Can Independently Alter Lipid Homeostasis In Offspring And Promote Metabolic Impairment After New Challenge To High-fat Diet

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Nutritional status in early life is critically involved in the metabolic phenotype of offspring. However the changes triggered by maternal consumption of high-fat diet (HFD) in pre- or postnatal period should be better understood. Here we evaluated whether maternal HFD consumption during gestation and lactation could differently affect liver miR-122 and miR-370 expression leading to metabolic damages observed in offspring. Moreover, we investigate whether early overnutrition program offspring to more harmful response to HFD in later life. Methods: Female mice were fed either a standard chow (SC) diet or a HFD three weeks before and during mating, gestation and/or lactation. Offspring were evaluated on the delivery day (d0), in a cross-fostering model at day 28 (d28) and in adult life, after a re-challenge with a HFD (d82). Results: In vitro analysis using liver cell line showed that palmitate could induced decrease in miR-122 and increase in miR-370 expression. Newborn pups (d0) from obese dams showed a decrease in lipid oxidation markers (Cpt1a and Acadvl), an increase in triacylglycerol synthesis markers (Agpat and Gpam), as well as lower miR-122 and higher miR-370 hepatic content that was inversely correlated to maternal serum NEFA and TAG. Pups fostered to SC dams presented an increase in body weight and Agpat/Gpam expression at d28 compared to pups fostered to HFD dams and an inverse correlation was observed between miR-122 hepatic expression and offspring serum TAG. In adult life (d82), the reintroduction of HFD resulted in higher body weight gain and hepatic lipid content. These effects were accompanied by impairment in lipid and glucose metabolism, demonstrated by reduced Cpt1a/Acadvl and increased Agpat/Gpam expression, lower glucose tolerance and insulin sensitivity. Conclusion: Our data suggest that both gestational and lactation overnutrition results in metabolic changes that can permanently alter lipid homeostasis in offspring. The presence of fatty acids in maternal blood and milk seem to be responsible for modulating the expression of miR-122 and miR-370, which are involved in liver metabolism. These alterations significantly increase susceptibility to obesity and ectopic lipid accumulation and lead to a more harmful response to HFD in offspring.14Sao Paulo Research Foundation (FAPESP) [2011/22156-7, 2013/07607-8, 2014/18165-9]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Curva de hemoglobina em um grupo de gestantes normais

Through hemoglobin determinations made in various stages of pregnancy, in 701 pregnant women with no iron supplementation ad hoc chosen out of a number of 7050 in the period from 1947 to 1969, a curve was constructed with the average rate of hemoglobin, which gave evidence of a drop that reaches its maximum around the 7th month of pregnancy and rises from that moment on. From this a working graph was built up and then it was discussed its importance in the diagnostic and treatment in anemia in pregnancy.Através das dosagens de hemoglobina realizadas em várias épocas da gravidez, em 701 gestantes sem suplementação de ferro escolhidas por amostragem casual simples de um universo de 7050 no período de 1947 a 1969, foi construída uma curva com as taxas médias de hemoglobina, que evidenciou uma queda que atinge o máximo por volta do 7.° mês de gravidez e elevando-se a partir desta época. A partir dela foi construída uma curva operacional e discutida a sua importância no diagnóstico e conduta frente a anemia na gravidez

Relação entre estado nutricional da gestante, fumo durante a gravidez, crescimento fetal e no primeiro ano de vida

The relationship between maternal nutritional state, maternal cigarette smoking habits, weight of infants at birth and their growth in the first year of life, in a group of 1,066 pregnant women (and their children) of low socio-economic status was studied. Babies born to smoking mothers weighed significantly less than those born to non-smoking mothers, whether these were normal or even obese women. It was also observed that children born to undernourished mothers weighed significantly less than those born to normal or obese women. Children born to smoking mothers weighed less than the others up to the 3rd month of life only; children born to undernourished women weighed significantly less than the others up to the 9th month of life. Thus, even among pregnant women of low socio-economic status, the effect of smoking on growth is restricted to the intra-uterine environment. The influence of maternal malnutrition is mantained for a longer period in this sample of the population. It was verified that there was a negative association between maternal nutritional status and maternal smoking habits, suggesting that, at least partially, the influence of maternal smoking on the fetus can be mediated by the nutritional status.Estudou-se a relação entre estado nutricional e hábito de fumar maternos, peso do recém-nascido ao nascer e crescimento no primeiro ano de vida num grupo de 1.066 gestantes de baixo nível sócio-econômico. Os filhos de mulheres fumantes apresentaram pesos significativamente menores que os filhos de não-fumantes, quer fossem suas mães, normais ou obesas. Também foi possível verificar que filhos de mulheres desnutridas pesaram significativamente menos que filhos de mulheres normais e estes que os de obesas. O prejuízo no peso dos filhos de mulheres fumantes manteve-se apenas até os 3 meses de idade, ao passo que até os 9 meses os filhos de mulheres desnutridas pesaram significativamente menos que as demais crianças, mostrando que, mesmo em gestantes de baixa renda, o efeito do fumo sobre o crescimento se restringe ao ambiente intra-uterino. Já o efeito da desnutrição materna é mais duradouro nessa população. Verificou-se que houve uma associação negativa entre estado nutricional e hábito de fumar maternos, sugerindo que, ao menos em parte, o efeito do tabagismo materno sobre o concepto pode ser intermediado pelo estado nutricional

Exercise During Pregnancy Protects Adult Mouse Offspring From Diet-induced Obesity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Background: Physical exercise induces positive alterations in gene expression involved in the metabolism of obesity. Maternal exercise provokes adaptations soon after birth in the offspring. Here, we investigated whether adult mouse offspring of swim-trained mothers is protected against the development of the deleterious effects of high fat diet (HFD). Methods: Our study comprises two parts. First, female C57BL/6 mice were divided into one sedentary and one swim-trained group (before and during pregnancy, n = 18). In the second part, adult offspring (n = 12) of trained and sedentary mothers was challenged to HFD for 16 weeks. Notably, most of the analysis was done in male offspring. Results: Our results demonstrate that maternal exercise has several beneficial effects on the mouse offspring and protects them from the deleterious effects of HFD in the adult. Specifically, swimming during pregnancy leads to lower birth weight in offspring through 2 months of age. When subjected to HFD for 4 month in the adulthood, our study presents novel data on the male offspring's metabolism of trained mothers. The offspring gained less weight, which was accompanied by less body fat, and they used more calories during daytime compared with offspring of sedentary mothers. Furthermore, we observed increased adiponectin expression in skeletal muscle, which was accompanied by decreased leptin levels and increased insulin sensitivity. Decreased interleukin-6 expression and increased peptide PYY levels were observed in sera of adult offspring of mothers that swam during pregnancy. Conclusions: Our results point to the conclusion that maternal exercise is beneficial to protect the offspring from developing obesity, which could be important for succeeding generations as well.12Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [2013/04757-9

Estado nutricional e hábito de fumar maternos, crescimento intra-uterino e pós-natal

In order to study the relationship between cigarette smoking, nutritional state during pregnancy, the birth weight of infants and their growth during the first year of life, a retrospective study was performed based on data collected in a pediatric clinic. The results showed that children of mal-nourished women have weights and heights lower than children of normal and overweight pregnant women, and that children born to smoking mothers were smaller and thinner when compared to children born to non-smoking mothers. The authors also discovered that these differences almost disappeared by the end of the first year of life, that is to say, the gestational influence in útero did not result in postnatal growth retardation.Com a finalidade de conhecer as relações entre o hábito de fumar, o estado nutricional de gestantes, o peso do recém-nascido e seu crescimento no primeiro ano de vida, foi feito um estudo retrospectivo com dados obtidos nos prontuários de crianças atendidas em um consultório pediátrico. Verificou-se que filhos de desnutridas tiveram peso e altura inferiores quando comparados aos filhos de normais e obesas, e que filhos de fumantes também tiveram peso e altura inferiores, quando comparados aos filhos de não fumantes. Pôde-se constatar, ainda, que ao final do primeiro ano de vida essas diferenças praticamente desapareciam, mostrando que as influências maternas in utero não tiveram como conseqüência um retardo de crescimento pós-natal

Hypothalamic S1p/s1pr1 Axis Controls Energy Homeostasis In Middle-aged Rodents: The Reversal Effects Of Physical Exercise

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Recently, we demonstrated that the hypothalamic S1PR1/STAT3 axis plays a critical role in the control of food consumption and energy expenditure in rodents. Here, we found that reduction of hypothalamic S1PR1 expression occurs in an age-dependent manner, and was associated with defective thermogenic signaling and weight gain. To address the physiological relevance of these findings, we investigated the effects of chronic and acute exercise on the hypothalamic S1PR1/STAT3 axis. Chronic exercise increased S1PR1 expression and STAT3 phosphorylation in the hypothalamus, restoring the anorexigenic and thermogenic signals in middle-aged mice. Acutely, exercise increased sphingosine-1-phosphate (S1P) levels in the cerebrospinal fluid (CSF) of young rats, whereas the administration of CSF from exercised young rats into the hypothalamus of middle-aged rats at rest was sufficient to reduce the food intake. Finally, the intracerebroventricular (ICV) administration of S1PR1 activators, including the bioactive lipid molecule S1P, and pharmacological S1PR1 activator, SEW2871, induced a potent STAT3 phosphorylation and anorexigenic response in middle-aged rats. Overall, these results suggest that hypothalamic S1PR1 is important for the maintenance of energy balance and provide new insights into the mechanism by which exercise controls the anorexigenic and thermogenic signals in the central nervous system during the aging process.91156169Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [FAPESP2011/09656-0, 2011/13828-1]Conselho Nacional de desenvolvimento cientifico e tecnologico (CNPq) [304815/2014-4]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq