Diminished insulin sensitivity is associated with altered brain activation to food cues and with risk for obesity - Implications for individuals born small for gestational age.

While classically linked to memory, the hippocampus is also a feeding behavior modulator due to its multiple interconnected pathways with other brain regions and expression of receptors for metabolic hormones. Here we tested whether variations in insulin sensitivity would be correlated with differential brain activation following exposure to palatable food cues, as well as with variations in implicit food memory in a cohort of healthy adolescents, some of whom were born small for gestational age (SGA). Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was positively correlated with activation in the cuneus, and negatively correlated with activation in the middle frontal lobe, superior frontal gyrus and precuneus when presented with palatable food images versus non-food images in healthy adolescents. Additionally, HOMA-IR and insulinemia were higher in participants with impaired food memory. SGA individuals had higher snack caloric density and greater chance for impaired food memory. There was also an interaction between the HOMA-IR and birth weight ratio influencing external eating behavior. We suggest that diminished insulin sensitivity correlates with activation in visual attention areas and inactivation in inhibitory control areas in healthy adolescents. Insulin resistance also associated with less consistency in implicit memory for a consumed meal, which may suggest lower ability to establish a dietary pattern, and can contribute to obesity. Differences in feeding behavior in SGA individuals were associated with insulin sensitivity and hippocampal alterations, suggesting that cognition and hormonal regulation are important components involved in their food intake modifications throughout life.

Impulsivity influences food intake in women with generalized anxiety disorder

Objective: Eating behavior is affected by psychological and neurocognitive factors. However, little is known about this relationship in anxious patients. Our aim was to investigate the associations between impulsivity, inhibitory control, energy-dense food consumption, and body mass index (BMI) in women with generalized anxiety disorder (GAD). Methods: In this cross-sectional study, 51 adult females with GAD answered the Barratt Impulsiveness Scale (BIS-11) and participated in a go/no-go task using food images. Anthropometric measurements were evaluated. A food frequency questionnaire and a snack test were used to study eating behavior. Pearson correlation and multiple linear regression were performed to analyze the variables of interest, adjusted by age. Results: Impulsivity predicted intake of sugar (p = 0.016, 95%CI 0.67-6.05), total fat (p = 0.007, 95%CI 0.62-3.71), and saturated fat (p = 0.004, 95%CI 0.30-1.48). The snack test showed a positive correlation between presence of impulsivity and intake of biscuits (R = 0.296; p = 0.051). Response inhibition to food images in the go/no-go task paradigm did not predict BMI or food intake. Conclusion: Impulsivity was predictive of higher sugar and saturated fat intake in women diagnosed with GAD. Our findings add to the literature regarding the association between neuropsychological factors and food consumption in this specific population.

Impulsivity influences food intake in women with generalized anxiety disorder.

OBJECTIVE: Eating behavior is affected by psychological and neurocognitive factors. However, little is known about this relationship in anxious patients. Our aim was to investigate the associations between impulsivity, inhibitory control, energy-dense food consumption, and body mass index (BMI) in women with generalized anxiety disorder (GAD). METHODS: In this cross-sectional study, 51 adult females with GAD answered the Barratt Impulsiveness Scale (BIS-11) and participated in a go/no-go task using food images. Anthropometric measurements were evaluated. A food frequency questionnaire and a snack test were used to study eating behavior. Pearson correlation and multiple linear regression were performed to analyze the variables of interest, adjusted by age. RESULTS: Impulsivity predicted intake of sugar (p = 0.016, 95%CI 0.67-6.05), total fat (p = 0.007, 95%CI 0.62-3.71), and saturated fat (p = 0.004, 95%CI 0.30-1.48). The snack test showed a positive correlation between presence of impulsivity and intake of biscuits (R = 0.296; p = 0.051). Response inhibition to food images in the go/no-go task paradigm did not predict BMI or food intake. CONCLUSION: Impulsivity was predictive of higher sugar and saturated fat intake in women diagnosed with GAD. Our findings add to the literature regarding the association between neuropsychological factors and food consumption in this specific population.

Early environmental influences on the development of children's brain structure and function.

The developing brain in utero and during the first years of life is highly vulnerable to environmental influences. Experiences occurring during this period permanently modify brain structure and function through epigenetic modifications (alterations of the DNA structure and chromatin function) and consequently affect the susceptibility to mental disorders. In this review, we describe evidence linking adverse environmental variation during early life (from the fetal period to childhood) and long-term changes in brain volume, microstructure, and connectivity, especially in amygdala and hippocampal regions. We also describe genetic variations that moderate the impact of adverse environmental conditions on child neurodevelopment, such as polymorphisms in brain-derived neurotrophic factor and catechol-O-methyltransferase genes, as well as genetic pathways related to glutamate and monoaminergic signaling. Lastly, we have depicted positive early life experiences that could benefit childhood neurodevelopment and reverse some detrimental effects of adversity in the offspring. WHAT THIS PAPER ADDS: Prenatal, peripartum, and postnatal adversities influence child behavior and neurodevelopment. Exposure to environmental enrichment and positive influences may revert these effects. Putative mechanisms involve alterations in neurotrophic factors and neurotransmitter systems. New tools/big data improved the understanding on how early adversity alters neurodevelopment. This permits better translation/application of the findings from animal models to humans.

INFLUENCIAS AMBIENTALES TEMPRANAS EN EL DESARROLLO DE LA ESTRUCTURA Y FUNCIÓN DEL CEREBRO DE LOS NIÑOS: El cerebro en desarrollo en el útero y durante los primeros años de vida es altamente vulnerable a las influencias ambientales. Las experiencias que se producen durante este período modifican permanentemente la estructura y función del cerebro a través de modificaciones epigenéticas (alteraciones de la estructura del ADN y la función de la cromatina) y, por consiguiente, afectan la susceptibilidad a los trastornos mentales. En esta revisión, describimos la evidencia que vincula la variación ambiental adversa durante la vida temprana (desde el período fetal hasta la infancia) y los cambios a largo plazo en el volumen cerebral, la microestructura y la conectividad, especialmente en las regiones de la amígdala y el hipocampo. También describimos variaciones genéticas que moderan el impacto de las condiciones ambientales adversas en el desarrollo neurológico infantil, como los polimorfismos en los genes del factor neurotrófico derivado del cerebro y de la catecol-O-metiltransferasa, así como las vías genéticas relacionadas con el glutamato y la señalización monoaminérgica. Por último, hemos descrito experiencias positivas de la vida temprana que podrían beneficiar el desarrollo neurológico infantil y revertir algunos efectos perjudiciales de la adversidad en la descendencia.

INFLUÊNCIAS AMBIENTAIS PRECOCES NO DESENVOLVIMENTO DA ESTRUTURA E FUNÇÃO CEREBRAL EM CRIANÇAS: O cérebro em desenvolvimento no útero e durante os primeiros anos devida é altamente vulnerável a influências ambientais. Experiências que ocorrem durante este período modificam permanentemente a estrutura e função cerebrais por meio de modificações epigenéticas (alterações da estrutura do DNA e função da cromatina). Consequentemente, afetam a suscetibilidade a desordens mentais. Nesta revisão, nós descrevemos a evidência relacionando variação ambiental adversa durante o início da vida (do período fetal à infância) e mudanças de longo prazo no volume, microestrutura e conectividade cerebral, especialmente nas regiões da amídala e hipocampo. Também descrevemos variações genéticas que moderam o impacto de condições ambientais adversas no neurodesenvolvimento infantil, tais como polimorfismos em fatores neurotróficos derivados do cérebro, e genes catechol-O-metiltransferases, assim como vias genéticas ligadas à sinalização por glutamato e momonoaminérgica. Por fim, descrevemos experiências precoces positivas que podem beneficiar o neurodesenvolvimento infantil e reverter alguns efeitos detrimentais da adversidade na prole.

Neonatal handling alters maternal emotional response to stress.

Neonatal handling is an experimental procedure used to analyze the effects of environmental interventions during early postpartum days (PPD). Long-lasting effects of repeated stress exposure in the neonatal period on the maternal side are poorly studied in this model. The aim of this study was to verify if handling the pups induces enduring effects on damsstress responses, increasing their risk for depression. Dams were divided into two groups (NH-Non-handled and H-Handled) based on the handling procedure (pups were handled for 1 min/per day from PPD1-PPD10) and then subdivided into four groups (NH, NH + S, H, and H + S) based on the exposure or not to restraint stress after weaning (1 hr/per day for 7 days, PPD22-PPD28). We analyzed damsbehavior in the forced swimming test (FST PPD29-PPD30), plasma basal corticosterone and BDNF levels, as well as adrenal weight (PPD31). The results show that handling alters the stress response of dams to acute and chronic stress, as evidenced by dams of the H group having increased immobility in the first day of FST (p < .001), similar to NH + S (p < .01). Dams of the H and H + S groups show decreased levels of corticosterone when compared to NH and NH + S groups (p < .05), but the H + S group shows an increased adrenal weight, suggesting an increased sensibility of the maternal organism to the chronic stress applied after weaning (p < .05). We show that handling may induce a long-lasting effect on maternal stress response; these changes in the damsemotional reactivity increase their susceptibility for the development of psychiatric disorders such as depression. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58: 614-622, 2016.

Genetic Differential Susceptibility to Socioeconomic Status and Childhood Obesogenic Behavior: Why Targeted Prevention May Be the Best Societal Investment.

IMPORTANCE: Genes may work by modulating the way individuals respond to environmental variation, and these discrete and differential genes vs environmental interactions may not be readily captured in simple association studies. OBJECTIVE: To determine whether children carrying the 7-repeat allele of the DRD4 gene living under adverse economic conditions have worse-than-average fat intake compared with those living in a healthy environment. DESIGN, SETTING, AND PARTICIPANTS: Data from an established prospective birth cohort (Maternal Adversity, Vulnerability, and Neurodevelopment) were used to study 4-year-old children from Montreal, Quebec, Canada and Hamilton, Ontario, Canada. A total of 190 children (94 girls and 96 boys) had height and weight measured and complete food diaries and were therefore eligible for the study. The study is derived from a birth cohort started in June 2003 and still ongoing. The last age of follow-up was at 6 years. EXPOSURES: Social environment was characterized based on the gross family income, and DNA was genotyped for the 7-repeat allele of the DRD4 gene. MAIN OUTCOMES AND MEASURES: Fat intake. RESULTS: The 5 steps to distinguish the differential susceptibility from other types of interaction were followed, and the study confirms that differential susceptibility is a relevant model to address the association between the 7-repeat allele of DRD4 and food choices in girls. Of the 190 children, 112 did not have the DRD4 7-repeat allele and 78 did. Baseline characteristics did not differ in these 2 groups. Although not different in several confounders, such as maternal educational level, maternal smoking during gestation, birth weight, and breastfeeding duration, girls carrying the 7-repeat allele of the DRD4 gene and living in adverse socioeconomic conditions have increased fat intake compared with girls who are noncarriers (DRD4 7+ mean, 33.95% of calories derived from fat; 95% CI, 28.76%-39.13%; DRD4 7- mean, 28.76%; 95% CI, 26.77%-30.83%). However, girls carrying the 7-repeat allele of the same gene and living in better socioeconomic conditions have decreased fat intake compared with noncarriers (DRD4 7+ mean, 29.03% of calories derived from fat; 95% CI, 26.69%-31.51%; DRD4 7- mean, 31.88%; 95% CI, 30.28%-33.58%). CONCLUSIONS AND RELEVANCE: Alleles previously considered to be obesity risk alleles might in fact function as plasticity alleles, determining openness to environmental modification and/or intervention, as seen in the girls in this study. This finding has important implications for obesity prevention and social pediatrics.

Transgenerational effects of maternal care interact with fetal growth and influence attention skills at 18 months of age.

BACKGROUND: Evidence suggests that there is an association between being born small for gestational age (SGA) and an increased risk of internalizing and externalizing problems, such as ADHD. Additionally, individuals who report having received a lower quality of maternal care show an increased prevalence of depression and anxiety, and they are generally worse caregivers of their offspring. Therefore, an interaction between the birth weight status and the quality of maternal care perceived by the mother could affect behavioral outcomes of the children. AIMS: Evaluate the influence of being born SGA and parental bonding, as perceived by the mother during her infancy, on the children's behavior at 18 months of age. STUDY DESIGN: Nested cross-sectional study within a Canadian prenatal cohort (MAVAN, Maternal Adversity, Vulnerability and Neurodevelopment) recruited from 2003 to 2010. SUBJECTS: Data from 305 children who were evaluated at 18 months of age. OUTCOME MEASURES: Early Childhood Behavior Questionnaire--ECBQ and Infant-Toddler Social and Emotional Assessment--ITSEA) were included. RESULTS: Children born SGA whose mothers reported low maternal care during her infancy (using the Parental Bonding Instrument--PBI) showed lower scores in the attentional set shifting trait (ECBQ, p=0.002) and attention construct (ITSEA, p=0.05) at 18 months of age. We also found that SGA increases decreases cuddliness (p=0.011) and poor perceived maternal care decreases low intensity pleasure (p=0.016) on the ECBQ. CONCLUSIONS: These findings suggest a complex transgenerational transmission whereby mother's own care interacts with the fetal growth of her offspring to predict its attentional skills at 18 months of age.

Grau de escolaridade materna e baixo peso ao nascer: uma meta-análise / Maternal education level and low birth weight: a meta-analysis

OBJETIVO: Analisar a associação entre grau de escolaridade materna e peso de nascimento, considerando-se a hipótese de que a utilização em excesso das tecnologias na área da saúde, assim como a escassez de recursos, pode produzir desfechos similares. MÉTODOS: Realizou-se uma meta-análise com estudos transversais e de coorte, selecionados por revisão sistemática na base de dados bibliográficos MEDLINE com os descritores: socioeconomic factors; infant, low birth weight; cohort studies; cross-sectional studies. As medidas de sumário de efeito foram obtidas pelo modelo de efeito aleatório, e os seus resultados apresentados por intermédio dos gráficos Forest Plot. O viés de publicação foi analisado pelo Teste de Egger, e a avaliação da qualidade dos estudos utilizou a Escala de Newcastle-Ottawa. RESULTADOS: A busca inicial encontrou 729 artigos. Destes, foram excluídos 594, após a leitura do título e do resumo; 21, após reuniões de consenso entre os três revisores; 102, após leitura do texto completo; e três, por não possuírem o desfecho adequado. Dos nove artigos finais, 88,8% apresentavam uma qualidade igual ou superior a seis estrelas (Escala de Newcastle-Ottawa), configurando boa qualidade aos estudos. A heterogeneidade dos artigos foi considerada moderada. A escolaridade materna elevada mostrou um efeito protetor de 33% sobre o baixo peso ao nascer, enquanto que o grau médio não apresentou proteção significativa, quando comparados à escolaridade materna baixa. CONCLUSÕES: A hipótese de similaridade entre os graus extremos da distribuição social, traduzidas pelo nível de escolaridade materna, em relação à proporção de baixo peso ao nascer, não foi confirmada.

OBJECTIVE: To assess the association between maternal education level and birth weight, considering the circumstances in which the excess use of technology in healthcare, as well as the scarcity of these resources, may result in similar outcomes. METHODS: A meta-analysis of cohort and cross-sectional studies was performed; the studies were selected by systematic review in the MEDLINE database using the following key words: socioeconomic factors, infant, low birth weight, cohort studies, cross-sectional studies. The summary measures of effect were obtained by random effect model, and its results were obtained through forest plot graphs. The publication bias was assessed by Egger’s test, and the Newcastle-Ottawa scale was used to assess study quality. RESULTS: The initial search found 729 articles. Of these, 594 were excluded after reading the title and abstract; 21, after consensus meetings among the three reviewers; 102, after reading the full text; and three for not having the proper outcome. Of the nine final articles, 88.8% had quality > six stars (Newcastle-Ottawa Scale), showing good quality studies. The heterogeneity of the articles was considered moderate. High maternal education showed a 33% protective effect against low birth weight, whereas medium degree of education showed no significant protection when compared to low maternal education. CONCLUSIONS: The hypothesis of similarity between the extreme degrees of social distribution, translated by maternal education level in relation to the proportion of low birth weight, was not confirmed.

Maternal education level and low birth weight: a meta-analysis.

OBJECTIVE: To assess the association between maternal education level and birth weight, considering the circumstances in which the excess use of technology in healthcare, as well as the scarcity of these resources, may result in similar outcomes. METHODS: A meta-analysis of cohort and cross-sectional studies was performed; the studies were selected by systematic review in the MEDLINE database using the following Key**words socioeconomic factors, infant, low birth weight, cohort studies, cross-sectional studies. The summary measures of effect were obtained by random effect model, and its results were obtained through forest plot graphs. The publication bias was assessed by Egger's test, and the Newcastle-Ottawa scale was used to assess study quality. RESULTS: The initial search found 729 articles. Of these, 594 were excluded after reading the title and abstract; 21, after consensus meetings among the three reviewers; 102, after reading the full text; and three for not having the proper outcome. Of the nine final articles, 88.8% had quality ≥ six stars (Newcastle-Ottawa Scale), showing good quality studies. The heterogeneity of the articles was considered moderate. High maternal education showed a 33% protective effect against low birth weight, whereas medium degree of education showed no significant protection when compared to low maternal education. CONCLUSIONS: The hypothesis of similarity between the extreme degrees of social distribution, translated by maternal education level in relation to the proportion of low birth weight, was not confirmed.

Early life stress interacts with the diet deficiency of omega-3 fatty acids during the life course increasing the metabolic vulnerability in adult rats.

Early stress can cause metabolic disorders in adulthood. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) deficiency has also been linked to the development of metabolic disorders. The aim of this study was to assess whether an early stressful event such as maternal separation interacts with the nutritional availability of n-3 PUFAs during the life course on metabolic aspects. Litters were randomized into: maternal separated (MS) and non-handled (NH). The MS group was removed from their dam for 3 hours per day and put in an incubator at 32 °C on days 1° to 10° postnatal (PND). On PND 35, males were subdivided into diets that were adequate or deficient in n-3 PUFAs, and this intervention was applied during the subsequent 15 weeks. Animal's body weight and food consumption were measured weekly, and at the end of the treatment tissues were collected. MS was associated with increased food intake (p = 0.047) and weight gain (p = 0.012), but no differences were found in the NPY hypothalamic content between the groups. MS rats had also increased deposition of abdominal fat (p<0.001) and plasma triglycerides (p = 0.018) when compared to the NH group. Interactions between early life stress and n-3 PUFAs deficiency were found in plasma insulin (p = 0.033), HOMA index (p = 0.049), leptin (p = 0.010) and liver PEPCK expression (p = 0.050), in which the metabolic vulnerability in the MS group was aggravated by the n-3 PUFAs deficient diet exposure. This was associated with specific alterations in the peripheral fatty acid profile. Variations in the neonatal environment interact with nutritional aspects during the life course, such as n-3 PUFAs diet content, and persistently alter the metabolic vulnerability in adulthood.

Preliminary evidence for an impulsivity-based thrifty eating phenotype.

INTRODUCTION: Low birth weight is associated with obesity and an increased risk for metabolic/cardiovascular diseases in later life. RESULTS: The results of the snack delay test, which encompassed four distinct trials, indicated that the gender × intrauterine growth restriction (IUGR) × trial interaction was a predictor of the ability to delay the food reward (P = 0.002). Among children with normal birth weights, girls showed a greater ability to delay food rewards than did boys (P = 0.014).In contrast, among children with IUGR, there was no such differential ability between girls and boys. Furthermore, in girls, impulsive responding predicted both increased consumption of palatable fat (P = 0.007) and higher BMIs (P = 0.020) at 48 mo of age, although there was no such association with BMI at 36 mo. DISCUSSION: In girls, the quality of fetal growth may contribute to impulsive eating, which may promote an increased intake of fats and consequently higher BMIs. As with the original thrifty phenotype, such a mechanism would be adaptive when food supplies are sparse, but would be problematic in societies with ample access to calorically rich foods. METHODS: We examined whether the quality of intrauterine growth programs obesogenic eating behaviors, by investigating (i) the relationship between birth weight and impulsive eating in 3-year-old children (using the snack delay test), and (ii) whether impulsive eating predicts fat intake and/or BMI at 4 years of age (using a laboratory-based test meal).

Maternal depression model: long-lasting effects on the mother following separation from pups.

This study was carried out to ascertain the effects of maternal separation (3 h per day) of mothers from their pups in the neonatal period in rats, which has been suggested to induce a depressive-like state, would have long lasting effects on different parameters including hippocampal Na(+), K(+)-ATPase activity, NO production, free radical production and antioxidant enzymes activities in dams. Fourty-eight Wistar rats were divided into 3 groups: control, brief separation (10 min) and long separation (3 h). The neonatal interventions were done on postpartum days 1-10. At 35 days post-partum the dams were killed and the hippocampal Na(+), K(+)-ATPase activity were measured, as well as the activity of the antioxidant enzymes catalase, glutathione peroxidase, superoxide dismutase, free radicals production, and the production of nitric oxide. Hippocampal Na(+), K(+)-ATPase activity was decreased in the brief separated group and in dams subjected to 3 h separation from their pups. A reduction in nitric oxide levels in the hippocampus in dams of the long separated group was also observed. It is concluded that the withdrawal of pups from their mothers make the mothers more susceptible to the development of neurochemical alterations that could be related to depressive features.

Effects of a chronic exposure to a highly palatable diet and its withdrawal, in adulthood, on cerebral Na+,K+-ATPase and plasma S100B in neonatally handled rats.

We have previously demonstrated that early environment influences the metabolic response, affecting abdominal fat deposition in adult female rats exposed to a long-term highly caloric diet. In the present study, our goal was to verify the effects of the chronic exposure, in adulthood, to a highly palatable diet (chocolate) on cerebral Na+,K+-ATPase activity and S100B protein concentrations, and the response to its withdrawal in neonatally handled and non-handled rats. We measured the consumption of foods (standard lab chow and chocolate), body weight gain, S100B protein concentrations, as well as cerebral Na(+),K(+)-ATPase activity during chronic exposure and after chocolate withdrawal in adult female rats that had been exposed or not to neonatal handling (10 min/day, 10 first days of life). Non-handled rats chronically exposed to chocolate exhibited increased plasma S100B levels, but there was no difference in abdominal fat S100B concentration between groups. Chronic chocolate consumption decreased Na+,K+-ATPase activity in both amygdala and hippocampus in non-handled, but not in handled rats, and this effect disappeared after chocolate withdrawal. Non-handled animals also demonstrated increased frequency of head shaking in the open field after 24h of chocolate withdrawal in comparison to handled ones. These findings suggest that neonatal handling modifies the vulnerability to metabolic and brain alterations induced by chronic exposure to a highly palatable diet in adulthood.

The NMDA antagonist MK-801 induces hyperalgesia and increases CSF excitatory amino acids in rats: reversal by guanosine.

Excitatory amino acids (EAAs) and their receptors play a central role in the mechanisms underlying pain transmission. NMDA-receptor antagonists such as MK-801 produce antinociceptive effects against experimental models of chronic pain, but results in acute pain models are conflicting, perhaps due to increased glutamate availability induced by the NMDA-receptor antagonists. Since guanosine and riluzole have recently been shown to stimulate glutamate uptake, the aim of this study was to examine the effects of guanosine or riluzole on changes in nociceptive signaling induced by MK-801 in an acute pain model. Rats received an i.p. injection of vehicle, morphine, guanosine, riluzole or MK-801 or a combined treatment (vehicle, morphine, guanosine or riluzole+MK-801) and were evaluated in the tail flick test, or had a CSF sample drawn after 30 min. Riluzole, guanosine, and MK-801 (0.01 or 0.1 mg/kg) did not affect basal nociceptive responses or CSF EAAs levels. However, MK-801 (0.5 mg/kg) induced hyperalgesia and increased the CSF EAAs levels; both effects were prevented by guanosine, riluzole or morphine. Hyperalgesia was correlated with CSF aspartate and glutamate levels. This study provides additional evidence for the mechanism of action of MK-801, showing that MK-801 induces hyperalgesia with parallel increase in CSF EAAs levels.

Severe intrauterine growth restriction is associated with higher spontaneous carbohydrate intake in young women.

Intrauterine growth restriction (IUGR) is associated with metabolic disorders in adulthood. In rats, an early adverse environment alters food preferences in adult life. We investigated whether IUGR is associated with spontaneous macronutrient preferences in humans. Two thousand sixty-three participants from a Brazilian birth cohort were evaluated at 24 y of age using a food frequency questionnaire, physical examination, anthropometric measurements, and biochemical assays (glucose, insulin, cholesterol, and triglycerides). IUGR was defined by the birth weight ratio (BWR = birth weight/mean weight for gestational age). Individuals were classified as non growth restricted (BWR > or =0.85), moderately growth restricted (0.85 > BWR > or = 0.75), and severely growth restricted (BWR <0.75). Severe IUGR women consumed a greater carbohydrate to protein ratio, even after controlling for social variables. There was a continuous association between growth restriction and later carbohydrate to protein ratio consumption in women. Women from both IUGR groups had a larger waist to hip ratio (WHR). The prevalence of metabolic syndrome was comparable between the groups. IUGR women preferred carbohydrates to protein in their regular diet, suggesting that spontaneous food choices may precede the appearance and contribute to the risk for metabolic diseases in this group.

Developmental origins of health and disease (DOHaD).

OBJECTIVE: To present a new branch of scientific knowledge, known as the developmental origins of health and disease (DOHaD), covering its concepts, study methods and ethical considerations in addition to the prospects for this area of knowledge. SOURCES: A non-systematic review of the biomedical literature intended to identify historical and current references related to the subject under discussion. SUMMARY OF THE FINDINGS: Recent studies demonstrate associations between aggressions suffered during the initial phases of somatic development and amplified risk of chronic diseases throughout life, such as obesity, diabetes and cardiovascular diseases. A variety of models have been proposed in attempts to better explain these associations, such as the thrifty phenotype, programming and predictive adaptive response theories and the concept of match or mismatch. Some of the mechanisms possibly involved in these processes are: effects of the environment on gene expression, through epigenetic mechanisms; effects of hormonal signals transmitted to the fetus via the placenta or the newborn via lactation. CONCLUSIONS: DOHaD draws together information originating from many different areas of knowledge, proposing new investigative methodologies to elucidate the influence of adverse events that occur during early phases of human development on the pattern of health and disease throughout life. This new scientific field proposes new models of causality and of the mechanisms involved in the emergence and development of chronic diseases. The results of these investigations may result in a significant impact on the prevention of chronic diseases, and also on health promotion in different phases of life.

Origens desenvolvimentistas da saúde e da doença (DOHaD): [revisão] / Developmental origins of health and disease (DOHaD): [review]

OBJETIVO: Apresentar um novo ramo da ciência, denominado origens desenvolvimentistas da saúde e doença (DOHaD), abordando conceitos, métodos de estudo, aspectos éticos e perspectivas para essa área do conhecimento. FONTES DOS DADOS: Revisão não sistemática da literatura biomédica, com o intuito de obter referências históricas e atualizadas relacionadas com o tema em discussão. SÍNTESE DOS DADOS: Estudos recentes demonstram associações entre agravos ocorridos em fases iniciais do desenvolvimento somático e a amplificação do risco para doenças crônicas ao longo da vida, tais como obesidade, diabetes e doenças cardiovasculares. Diferentes modelos foram propostos na tentativa de melhor explicar essas associações, como a teoria do fenótipo poupador, a programação, as respostas adaptativas preditivas e o conceito de concordância ou contraste. Alguns dos possíveis mecanismos envolvidos nesses processos são: efeitos do ambiente sobre a expressão gênica, através de mecanismos epigenéticos; efeitos de sinais hormonais transmitidos ao feto através da placenta ou ao recém-nascido através da lactação. CONCLUSÕES: O DOHaD agrega informações advindas de várias áreas do conhecimento, propondo novas metodologias de investigação no sentido de esclarecer a influência de eventos adversos ocorridos em fases precoces do desenvolvimento humano sobre o padrão de saúde e doença ao longo da vida. Esse novo campo da ciência propõe novos modelos de causalidade e mecanismos envolvidos no surgimento e desenvolvimento de doenças crônicas. Os resultados dessas investigações poderão resultar em impacto significativo na prevenção de doenças crônicas, bem como na promoção de saúde em diferentes fases da vida.

OBJECTIVE: To present a new branch of scientific knowledge, known as the developmental origins of health and disease (DOHaD), covering its concepts, study methods and ethical considerations in addition to the prospects for this area of knowledge. SOURCES: A non-systematic review of the biomedical literature intended to identify historical and current references related to the subject under discussion. SUMMARY OF THE FINDINGS: Recent studies demonstrate associations between aggressions suffered during the initial phases of somatic development and amplified risk of chronic diseases throughout life, such as obesity, diabetes and cardiovascular diseases. A variety of models have been proposed in attempts to better explain these associations, such as the thrifty phenotype, programming and predictive adaptive response theories and the concept of match or mismatch. Some of the mechanisms possibly involved in these processes are: effects of the environment on gene expression, through epigenetic mechanisms; effects of hormonal signals transmitted to the fetus via the placenta or the newborn via lactation. CONCLUSIONS: DOHaD draws together information originating from many different areas of knowledge, proposing new investigative methodologies to elucidate the influence of adverse events that occur during early phases of human development on the pattern of health and disease throughout life. This new scientific field proposes new models of causality and of the mechanisms involved in the emergence and development of chronic diseases. The results of these investigations may result in a significant impact on the prevention of chronic diseases, and also on health promotion in different phases of life.

Could preference for palatable foods in neonatally handled rats alter metabolic patterns in adult life?

Previous studies indicate that, in adulthood, neonatally handled rats consume more sweet food than nonhandled rats. The aim of the present study was to assess the effects of the chronic exposure to a palatable diet (chocolate) in adult neonatally handled rats. We measured the consumption of foods (standard lab chow and chocolate), body weight gain, abdominal fat deposition, and levels of plasma lipids, glucose, insulin, and corticosterone in adult neonatally handled (10 min/d, first 10 d of life) and nonhandled rats. We found an increased intake of chocolate in handled rats, but this consumption decreased over time. Handled male animals exhibited higher body weight, higher caloric efficiency, and lower triglyceride levels. Nonhandled females that were exposed long-term to the highly caloric diet had increased abdominal fat deposition compared with handled females. Overall female rats had increased abdominal fat deposition, higher total cholesterol and glucose levels, and lower insulin in comparison with males. Interestingly, chocolate consumption diminished the weight of the adrenal glands in both handled and nonhandled animals. These findings suggest that neonatal handling induces a particular metabolic pattern that is sex specific.

Long-lasting delayed hyperalgesia after chronic restraint stress in rats-effect of morphine administration.

Different effects upon the nociceptive response have been observed with exposure to acute and chronic stress in rats. In the present study we repeatedly submitted rats to restraint for 40 days, inducing hyperalgesia using the tail-flick test. A new session of acute stress was applied at the end of 40 days period, and the chronically-stressed animals demonstrated analgesia after forced swimming, but not after restraint. The effect of stress interruption for 14 or 28 days on the nociceptive threshold was then investigated. The basal tail-flick latency remained decreased for at least 28 days (hyperalgesic effect). Following the periods of suspension, the animals were submitted to new session of acute restraint, and stress-induced analgesia was observed only after 28 days of stress interruption. Thus, the mechanisms involved in the long-lasting hyperalgesia presented in this study are not exactly the same as those responsible for the analgesia induced by acute stressors. After 40 days of chronic stress treatment, morphine was injected i.p. (1.0, 5.0 mg/kg or saline). The repeatedly stressed rats displayed decreased morphine effects on nociception compared to unstressed controls. The tolerance of the response to morphine agrees with previous studies suggesting that chronic restraint stress could modify the activity of opioid systems.