Genetically-predicted prefrontal DRD4 gene expression modulates differentiated brain responses to food cues in adolescent girls and boys.

The dopamine receptor 4 (DRD4) in the prefrontal cortex (PFC) acts to modulate behaviours including cognitive control and motivation, and has been implicated in behavioral inhibition and responsivity to food cues. Adolescence is a sensitive period for the development of habitual eating behaviors and obesity risk, with potential mediation by development of the PFC. We previously found that genetic variations influencing DRD4 function or expression were associated with measures of laboratory and real-world eating behavior in girls and boys. Here we investigated brain responses to high energy-density (ED) and low-ED food cues using an fMRI task conducted in the satiated state. We used the gene-based association method PrediXcan to estimate tissue-specific DRD4 gene expression in prefrontal brain areas from individual genotypes. Among girls, those with lower vs. higher predicted prefrontal DRD4 expression showed lesser activation to high-ED and low-ED vs. non-food cues in a distributed network of regions implicated in attention and sensorimotor processing including middle frontal gyrus, and lesser activation to low-ED vs non-food cues in key regions implicated in valuation including orbitofrontal cortex and ventromedial PFC. In contrast, males with lower vs. higher predicted prefrontal DRD4 expression showed minimal differences in food cue response, namely relatively greater activation to high-ED and low-ED vs. non-food cues in the inferior parietal lobule. Our data suggest sex-specific effects of prefrontal DRD4 on brain food responsiveness in adolescence, with modulation of distributed regions relevant to cognitive control and motivation observable in female adolescents.

Interaction of DRD2/ANKK1 Taq1A Genotype with in-Store Retail Food Environment Exposures on Diet Quality in a Cohort of Quebec Adults.

BACKGROUND/AIMS: Gene-environment interactions may be relevant for nutrition outcomes. This study assessed the interaction between DRD2/ANKK1 Taq1A genotype and exposures to in-store retail food environment on diet quality. METHODS: CARTaGENE biobank data (n = 3,532) were linked to provincial food retail data. The Canadian adaptation of the Healthy Eating Index 2010 (HEI-C) was calculated from food frequency questionnaires. Generalized linear models adjusted for sociodemographic factors, anthropometrics, and energy intake were used to assess interactions between the Taq1A variant and retail food measures. RESULTS: A significant inverse interaction was observed between Taq1A and ice cream store displays on HEI-C score (estimate: -15.46 [95% confidence interval (CI): -24.83, -6.10], p = 0.0012) where, among allele carriers, increasing exposure to ice cream displays was associated with a lower HEI-C score as compared to allele carriers with a lower exposure. A significant positive interaction between Taq1A and price of vegetables was also observed, where, among allele carriers, increasing exposure to a higher price was associated with a higher HEI-C score compared to allele carriers with exposure to a lower price (estimate: 2.46 [95% CI: 0.78, 4.14], p = 0.0041). The opposite pattern was observed among non-carriers. CONCLUSIONS: DRD2/ANKK1 Taq1A is associated with adaptive responses to ice cream displays and vegetable prices, suggesting a differential susceptibility to retail environment food cues.

Low birth weight is associated with increased fat intake in school-aged boys.

Evidence suggests that both high and low birth weight children have increased the risk for obesity and the metabolic syndrome in adulthood. Previously we have found altered feeding behaviour and food preferences in pre-school children and adults born with low birth weight. In this study, we investigated if birth weight was associated with different intake of fat, carbohydrate and/or protein at 6-12 years of age. This is a cross-sectional study where 255 guardians answered online and telephone questions including anthropometrics and demographic data, parental family food rules (food control, encouragement and restriction) and a complete web-based FFQ for their children (130 boys and 125 girls). Baseline demographic and parental food rules characteristics did not differ accordingly to sex. Linear regression models were conducted separately for each sex, adjusted for income, age and maternal age. There were no differences in total energy intake, but energy density (ED, energy content/g) was negatively associated with birth weight in boys. Macronutrient analysis showed that ED intake was from a greater intake of fat. Birth weight was not a significant predictor of protein and carbohydrate intake in boys. In girls, we saw a positive correlation between fat intake and cholesterol intake v. birth weight, but no association with ED intake (results did not remain after adjustment). The study shows that low birth weight is associated with altered fat intake in childhood in a sex-specific manner. It is likely that biological factors such as fetal programming of homoeostatic and/or hedonic pathways influencing food preferences are involved in this process.

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.

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).

Therapeutic use of omega-3 fatty acids in bipolar disorder.

Bipolar disorder (BD) is a severe, chronic affective disorder, associated with significant disability, morbidity and premature mortality. Omega-3 polyunsaturated fatty acids (PUFAs) play several important roles in brain development and functioning. Evidence from animal models of dietary omega-3 (n-3) PUFA deficiency suggest that these fatty acids are relevant to promote brain development and to regulate behavioral and neurochemical aspects related to mood disorders, such as stress responses, depression and aggression, as well as dopaminergic content and function. Preclinical and clinical evidence suggests roles for PUFAs in BD. n-3 PUFAs seem to be an effective adjunctive treatment for unipolar and bipolar depression, but further large-scale, well-controlled trials are needed to examine its clinical utility in BD. The use of n-3 as a mood stabilizer among BD patients is discussed here. This article summarizes the molecular pathways related to the role of n-3 as a neuroprotective and neurogenic agent, with a specific focus on BDNF. It is proposed that the n-3-BDNF association is involved in the pathophysiology of BD and represents a promising target for developing a novel class of rationally devised therapies.

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.