The impact of poor fetal growth and chronic hyperpalatable diet exposure in adulthood on hippocampal function and feeding patterns in male rats.

Poor fetal growth affects eating behavior and the mesocorticolimbic system; however, its influence on the hippocampus has been less explored. Brain insulin sensitivity has been linked to developmental plasticity in response to fetal adversity and to cognitive performance following high-fat diet intake. We investigated whether poor fetal growth and exposure to chronic hyperpalatable food in adulthood could influence the recognition of environmental and food cues, eating behavior patterns, and hippocampal insulin signaling. At 60 days of life, we assigned male offspring from a prenatal animal model of 50% food restriction (FR) to receive either a high-fat and -sugar (HFS) diet or standard chow (CON) diet. Behavioral tests were conducted at 140 days, then tissues were collected. HFS groups showed a diminished hippocampal pAkt/Akt ratio. FR-CON and FR-HFS groups had higher levels of suppressor of cytokine signaling 3, compared to control groups. FR groups showed increased exploration of a novel hyperpalatable food, independent of their diet, and HFS groups exhibited overall lower entropy (less random, more predictable eating behavior) when the environment changed. Poor fetal growth and chronic HFS diet in adulthood altered hippocampal insulin signaling and eating patterns, diminishing the flexibility associated with eating behavior in response to extrinsic changes in food availability in the environment.

Accumbal µ-opioid receptors and salt taste-elicited hedonic responses in a rodent model of prenatal adversity, and their correlates using human functional genomics.

Prenatal adversity is associated with behavioral obesogenic features such as preference for palatable foods. Salt appetite may play a role in the development of adiposity and its consequences in individuals exposed to prenatal adversity, and sodium consumption involves individual differences in accumbal µ-opioid receptors function. We investigated the hedonic responses to salt and the levels of µ-opioid receptors and tyrosine hydroxylase in the nucleus accumbens (Nacc) of pups from an animal model of prenatal dietary restriction. In children, we evaluated the interaction between fetal growth and the genetic background associated with the accumbal µ-opioid receptor gene (OPRM1) expression on sodium consumption during a snack test. Sprague-Dawley dams were randomly allocated from pregnancy day 10 to receive an ad libitum (Adlib) or a 50% restricted (FR) diet. The pups' hedonic responses to a salt solution (NaCl 2%) or water were evaluated on the first day of life. FR and Adlib pups differ in their hedonic responses to salt, and there were decreased levels of accumbal µ-opioid and p-µ-opioid receptors in FR pups. In humans, a test meal and genotyping from buccal epithelial cells were performed in 270 children (38 intrauterine growth restricted-IUGR) at 4 years old from a Canadian prospective cohort (MAVAN). The OPRM1 genetic score predicted the sodium intake in IUGR children, but not in controls. The identification of mechanisms involved in the brain response to prenatal adversity and its consequences in behavioral phenotypes and risk for chronic diseases later in life is important for preventive and therapeutic purposes.

Relationship between insulin and Netrin-1/DCC guidance cue pathway regulation in the prefrontal cortex of rodents exposed to prenatal dietary restriction.

Fetal restriction (FR) alters insulin sensitivity, but it is unknown how the metabolic profile associated with restriction affects development of the dopamine (DA) system and DA-related behaviors. The Netrin-1/DCC guidance cue system participates in maturation of the mesocorticolimbic DA circuitry. Therefore, our objective was to identify if FR modifies Netrin-1/DCC receptor protein expression in the prefrontal cortex (PFC) at birth and mRNA in adulthood in rodent males. We used cultured HEK293 cells to assess if levels of miR-218, microRNA regulator of DCC, are sensitive to insulin. To assess this, pregnant dams were subjected to a 50% FR diet from gestational day 10 until birth. Medial PFC (mPFC) DCC/Netrin-1 protein expression was measured at P0 at baseline and Dcc/Netrin-1 mRNA levels were quantified in adults 15 min after a saline/insulin injection. miR-218 levels in HEK-293 cells were measured in response to insulin exposure. At P0, Netrin-1 levels are downregulated in FR animals in comparison to controls. In adult rodents, insulin administration results in an increase in Dcc mRNA levels in control but not FR rats. In HEK293 cells, there is a positive correlation between insulin concentration and miR-218 levels. Since miR-218 is a Dcc gene expression regulator and our in vitro results show that insulin regulates miR-218 levels, we suggest that FR-induced changes in insulin sensitivity could be affecting Dcc expression via miR-218, impacting DA system maturation and organization. As fetal adversity is linked to nonadaptive behaviors later in life, this may contribute to early identification of vulnerability to chronic diseases associated with fetal adversity.

Emotional eating in women with generalized anxiety disorder.

INTRODUCTION: Individuals diagnosed with generalized anxiety disorder (GAD) seek pleasurable foods to avoid their negative emotional experiences. Ineffective regulation of negative emotions may be a risk factor for emotional eating (EE), leading to suffering, dysfunctional behaviors, and weight gain. OBJECTIVES: The aim of this study is to understand the relationship between emotional dysregulation and EE, investigating potential mediators such as the intensity of the worry, avoidance of internal experiences, mindfulness, and self-compassion in female patients with anxiety. METHODS: In this cross-sectional study, participants from a randomized clinical trial diagnosed with GAD answered the following instruments at baseline: the Difficulties in Emotion Regulation Scale (DERS), the Three Factor Eating Questionnaire (TFEQ-R21), the Penn State Worry Questionnaire (PSWQ), the Action and Acceptance Questionnaire (AAQ), the Five Facet Mindfulness Questionnaire (FFMQ), and the Self-Compassion Scale (SCS). We estimated Pearson correlation coefficients and performed mediation analyses. RESULTS: We evaluated 51 female individuals, 34 of whom completed all the questionnaires. Our data showed that EE was positively correlated with emotional dysregulation (r = 0.593; p < 0.001), worry trait (r = 0.402; p = 0.018), and avoidance of internal experiences (r = 0.565; p < 0.001), whereas it was negatively correlated with self-compassion (r = -0.590; p < 0.001) and mindful state (r = -0.383; p = 0.026). Moreover, we demonstrated that self-compassion mediates the relationship between emotional dysregulation and EE (ab product estimate = 0.043, 95% confidence interval [95%CI] 0.003-0.084). CONCLUSION: Our findings contribute to the literature by identifying psychological factors that could mediate the association between emotional dysregulation and EE, enabling identification of more effective eating behavior intervention targets for patients with GAD.

Nutrition risk prevalence and screening tools' validity in pediatric patients: A systematic review.

Nutrition screening (NS) allows health professionals to identify patients at nutritional risk (NR), enabling early nutrition intervention. This study aimed to systematically review the criterion validity of NS tools for hospitalized non-critical care pediatric patients and to estimate the prevalence of NR in this population. This research was performed using PubMed, Embase, and Scopus databases until June 2021. The reviewers extracted the studies' general information, the population characteristics, the NR prevalence, and the NS tools' concurrent and predictive validity data. Quality evaluation was performed using the Newcastle-Ottawa Scale, adapted Newcastle-Ottawa Scale, and Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). The primary studies were qualitatively analyzed, and descriptive statistics were calculated to describe the NR prevalence. Of the total 3944 studies found, 49 met the inclusion criteria. Ten different pediatric NS tools were identified; the most frequently used were Screening Tool for Risk on Nutritional Status and Growth (STRONGkids), Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP), and Pediatric Yorkhill Malnutrition Score (PYMS). The mean NR prevalence was 59.85% (range, 14.6%-96.9%). Among all NS tools analyzed, STRONGkids and PYMS showed the best diagnostic performance. STRONGkids had the most studies of predictive validity showing that the NR predicted a higher hospital length of stay (odds ratio [OR], 1.96-8.02), health complications during hospitalization (OR, 3.4), and the necessity for nutrition intervention (OR, 18.93). Considering the diagnostic accuracy, robust and replicated findings of predictive validity, and studies' quality, STRONGkids performed best in identifying NR in the pediatric population among the tools identified.

Emotional eating in women with generalized anxiety disorder

Abstract Introduction Individuals diagnosed with generalized anxiety disorder (GAD) seek pleasurable foods to avoid their negative emotional experiences. Ineffective regulation of negative emotions may be a risk factor for emotional eating (EE), leading to suffering, dysfunctional behaviors, and weight gain. Objectives The aim of this study is to understand the relationship between emotional dysregulation and EE, investigating potential mediators such as the intensity of the worry, avoidance of internal experiences, mindfulness, and self-compassion in female patients with anxiety. Methods In this cross-sectional study, participants from a randomized clinical trial diagnosed with GAD answered the following instruments at baseline: the Difficulties in Emotion Regulation Scale (DERS), the Three Factor Eating Questionnaire (TFEQ-R21), the Penn State Worry Questionnaire (PSWQ), the Action and Acceptance Questionnaire (AAQ), the Five Facet Mindfulness Questionnaire (FFMQ), and the Self-Compassion Scale (SCS). We estimated Pearson correlation coefficients and performed mediation analyses. Results We evaluated 51 female individuals, 34 of whom completed all the questionnaires. Our data showed that EE was positively correlated with emotional dysregulation (r = 0.593; p < 0.001), worry trait (r = 0.402; p = 0.018), and avoidance of internal experiences (r = 0.565; p < 0.001), whereas it was negatively correlated with self-compassion (r = -0.590; p < 0.001) and mindful state (r = -0.383; p = 0.026). Moreover, we demonstrated that self-compassion mediates the relationship between emotional dysregulation and EE (ab product estimate = 0.043, 95% confidence interval [95%CI] 0.003-0.084). Conclusion Our findings contribute to the literature by identifying psychological factors that could mediate the association between emotional dysregulation and EE, enabling identification of more effective eating behavior intervention targets for patients with GAD.

Thrifty-Eating Behavior Phenotype at the Food Court - Programming Goes Beyond Food Preferences.

Introduction: Prenatal growth impairment leads to higher preference for palatable foods in comparison to normal prenatal growth subjects, which can contribute to increased body fat mass and a higher risk for developing chronic diseases in small-for-gestational-age (SGA) individuals throughout life. This study aimed to investigate the effect of SGA on feeding behavior in children and adolescents, as well as resting-state connectivity between areas related to reward, self-control, and value determination, such as orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DL-PFC), amygdala and dorsal striatum (DS). Methods: Caregivers and their offspring were recruited from two independent cohorts in Brazil (PROTAIA) and Canada (MAVAN). Both cohorts included anthropometric measurements, food choice tasks, and resting-state functional magnetic resonance imaging (fMRI) data. Results: In the Brazilian sample (17 ± 0.28 years, n=70), 21.4% of adolescents were classified as SGA. They exhibited lower monetary-related expenditure to buy a snack compared to controls in the food choice test. Decreased functional connectivity (n=40) between left OFC and left DL-PFC; and between right OFC and: left amygdala, right DS, and left DS were observed in the Brazilian SGA participants. Canadian SGA participants (14.9%) had non-significant differences in comparison with controls in a food choice task at 4 years old ( ± 0.01, n=315). At a follow-up brain scan visit (10.21 ± 0.140 years, n=49), SGA participants (28.6%) exhibited higher connectivity between the left OFC and left DL-PFC, also higher connectivity between the left OFC and right DL-PFC. We did not observe significant anthropometric neither nutrients' intake differences between groups in both samples. Conclusions: Resting-state fMRI results showed that SGA individuals had altered connectivity between areas involved in encoding the subjective value for available goods and decision-making in both samples, which can pose them in disadvantage when facing food options daily. Over the years, the cumulative exposure to particular food cues together with the altered behavior towards food, such as food purchasing, as seen in the adolescent cohort, can play a role in the long-term risk for developing chronic non-communicable diseases.

Neonatal hypoxia-ischemia induces dysregulated feeding patterns and ethanol consumption that are alleviated by methylphenidate administration in rats.

Impulsivity, as observed in patients diagnosed with Attention-deficit/hyperactivity disorder (ADHD), can induce dysregulated behaviors such as binge eating and drug addiction. We previously demonstrated that neonatal hypoxia-ischemia (HI) resulted in ADHD-like behaviors in rats and that methylphenidate (MPH) administration (the first therapeutic option for ADHD) reversed these deficits. Here, we aimed at investigating addictive-like behaviors, such as the reward-based feeding behavior (using the BioDAQ monitor) and ethanol consumption (using the IA2BC procedure) in adult animals subjected to neonatal HI and treated with or without MPH. Male Wistar rats were divided into four groups (n = 10-12/group): control saline (CTS), CTMPH, HI saline (HIS) and HIMPH. The HI procedure was conducted at postnatal day (PND) 7 and behavioral analyses between PND 60-90, in which MPH (2.5 mg/kg, i.p.) was administered 30 min prior to each behavioral evaluation (6 sessions in BioDAQ and 12 sessions in the IA2BC protocol). HI animals had a dysregulated feeding intake shortly after eating a small piece of the palatable diet, and MPH reversed this dysregulated pattern. However, when the palatable diet was freely available, MPH stimulated a higher intake of this diet in the first exposure day, and this effect was potentialized in HIMPH rats. Increased ethanol intake was observed in HI rats, and MPH administration alleviated this behavior; contrarily, MPH treatment in control rats induced an increase in ethanol consumption. The present findings give additional support to the relationship between neonatal HI and ADHD but the differential response to MPH in control or HI animals highlights the importance of avoiding indiscriminate use of MPH by healthy individuals.

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.

Antioxidant Micronutrients and Essential Fatty Acids Supplementation on Cystic Fibrosis Outcomes: A Systematic Review.

BACKGROUND: Antioxidant micronutrients and essential fatty acids supplementation intake appears to have a protective effect in some diseases such as cardiovascular disease, cancer, and asthma. OBJECTIVE: The aim of this study was to perform a systematic review to evaluate the effects of these nutrients on nutritional and clinical outcomes of patients with cystic fibrosis (CF). METHODS: This is a systematic review of randomized clinical trials (RCTs) in CF. MEDLINE (via PubMed), Embase, and Scopus databases were searched for RCTs published from 1948 through February 2019. Two investigators independently reviewed the titles and abstracts and then extracted the data from the included studies using a standardized predesigned form. Two reviewers independently performed the quality assessment of the RCTs according to the Cochrane risk of bias tools. RESULTS: A total of 4,792 studies were identified, and 23 were eligible (8 antioxidant micronutrient and 15 essential fatty acids). The interventions found were beta-carotene, zinc, magnesium, multivitamin, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), linoleic acid and lipid matrix with choline supplementation. A significant improvement was observed in: (a) pulmonary function with magnesium (n=1) and essential fatty acids (n=2) supplementation; (b) less pulmonary exacerbations with beta-carotene (n=1), zinc (n=1), antioxidant-enriched multivitamin (n=1) and essential fatty acids (n=2) supplementation. One study with antioxidant-enriched multivitamin and four studies with EPA/DHA supplementation reported significant reductions in inflammatory markers. Nutritional status was not modified by antioxidants supplementation in any of the studies, while in five studies there was an improvement with fatty acids supplementation. The risk of bias of the majority of the parallel studies was high. CONCLUSIONS: The benefits of antioxidants or DHA/EPA supplementation for CF, although observed in some studies, are not consistent enough to recommend routine use of these supplements. The mechanisms of action of these nutrients, dose levels and timing should be further explored in future studies.

Intrauterine growth restriction increases impulsive behavior and is associated with altered dopamine transmission in both medial prefrontal and orbitofrontal cortex in female rats.

Recent studies have implicated a role for impulsivity in the altered eating behaviors and the increased risk for obesity consistently associated with intrauterine growth restriction (IUGR). Changes in dopamine transmission within prefrontal areas are believed to contribute to these adverse outcomes. Here we investigated the impulsive behavior toward a delayed reward and evaluated dopamine levels and its receptors in the medial prefrontal (mPFC) and orbitofrontal (OFC) cortex of female adult rats exposed to IUGR. From day 10 of pregnancy and until birth, Sprague-Dawley dams received either an ad libitum (Adlib) or a 50% food-restricted (FR) diet. At birth, all pups were adopted by Adlib mothers, generating the groups Adlib/Adlib (control) and FR/Adlib (intrauterine growth-restricted). Adult impulsive behavior was evaluated using a Tolerance to Delay of Reward Task. In vivo dopamine responses to sweet food intake were measured by voltammetry, and D1, D2 and DAT levels were accessed by Western Blot. Animals from FR group showed a pronounced aversion to delayed rewards. DA response to sweet food was found to be blunted in the mPFC of FR animals, whereas in the OFC, the DA levels appear to be unaffected by reward consumption. Moreover, FR animals presented reduced D1 receptors in the OFC and a later increase in the mPFC D2 levels. These findings suggest that IUGR female rats are more impulsive and that the associated mechanism involves changes in the dopamine signaling in both the mPFC and OFC.

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.

Is willingness to exercise programmed in utero? Reviewing sedentary behavior and the benefits of physical activity in intrauterine growth restricted individuals.

OBJECTIVE: The literature suggests that a fetus will adapt to surrounding adversities by optimizing its use of energy to improve survival, ultimately leading to the programming of the individual's energy intake and expenditure. While recent reviews focused on the fetal programming of energy intake and food preferences, there is also some evidence that fetal adversity is associated with diminished physical activity levels. Therefore, we aimed to review (a) the evidence for an association between being born with intrauterine growth restriction and sedentarism over the life-course and (b) the potential benefits of physical activity over cardiometabolic risk factors for this population. SOURCES: PubMed, Scielo, Scopus and Embase. SUMMARY OF FINDINGS: Most clinical studies that used objective measures found no association between intrauterine growth restriction and physical activity levels, while most studies that used self-reported questionnaires revealed such relationships, particularly leisure time physical activity. Experimental studies support the existence of fetal programming of physical activity, and show that exposure to exercise during IUGR individuals' life improves metabolic outcomes but less effect was seen on muscle architecture or function. CONCLUSIONS: Alterations in muscle strength and metabolism, as well as altered aerobic performance, may predispose IUGR individuals to be spontaneously less physically active, suggesting that this population may be an important target for preventive interventions. Although very heterogeneous, the different studies allow us to infer that physical activity may have beneficial effects especially for individuals that are more vulnerable to metabolic modifications such as those with IUGR.

Decreased comfort food intake and allostatic load in adolescents carrying the A3669G variant of the glucocorticoid receptor gene.

BACKGROUND: The A3669G single nucleotide polymorphism (SNP) of the glucocorticoid receptor (GR) gene NR3C1 is associated with altered tissue sensitivity to glucocorticoids (GCs). GCs modulate the food reward circuitry and are implicated in increased intake of palatable foods, which can lead to the metabolic syndrome and obesity. We hypothesized that presence of the G variant of the A3669G SNP would affect preferences for palatable foods and alter metabolic, behavioural, and neural outcomes. METHODS: One hundred thirty-one adolescents were genotyped for the A3669G polymorphism, underwent anthropometric assessment and nutritional evaluations, and completed behavioural measures. A subsample of 74 subjects was followed for 5 years and performed a brain functional magnetic resonance imaging (fMRI) paradigm to verify brain activity in response to food cues. RESULTS: Sugar and total energy consumption were lower in A3669G G allele variant carriers. On follow-up, this group also had reduced serum insulin concentrations, increased insulin sensitivity, and lower anxiety scores. Because of our unbalanced sample sizes (31/37 participants non-G allele carriers/total), our imaging data analysis failed to find whole brain-corrected significant results in between-group t-tests. CONCLUSION: These results highlight that a genetic variation in the GR gene is associated, at the cellular level, with significant reduction in GC sensitivity, which, at cognitive and behavioural levels, translates to altered food intake and emotional stress response. This genetic variant might play a major role in decreasing risk for metabolic and psychiatric diseases.

Gene and environment interaction: Is the differential susceptibility hypothesis relevant for obesity?

The differential susceptibility model states that a given genetic variant is associated with an increased risk of pathology in negative environments but greater than average resilience in enriched ones. While this theory was first implemented in psychiatric-genetic research, it may also help us to unravel the complex ways that genes and environments interact to influence feeding behavior and obesity. We reviewed evidence on gene vs. environment interactions that influence obesity development, aiming to support the applicability of the differential susceptibility model for this condition, and propose that various environmental "layers" relevant for human development should be considered when bearing the differential susceptibility model in mind. Mother-child relationship, socioeconomic status and individual's response are important modifiers of BMI and food intake when interacting with gene variants, "for better and for worse". While only a few studies to date have investigated obesity outcomes using this approach, we propose that the differential susceptibility hypothesis is in fact highly applicable to the study of genetic and environmental influences on feeding behavior and obesity risk.

Interaction between perceived maternal care, anxiety symptoms, and the neurobehavioral response to palatable foods in adolescents.

Studies in rodents have shown that early life trauma leads to anxiety, increased stress responses to threatening situations, and modifies food intake in a new environment. However, these associations are still to be tested in humans. This study aimed to verify complex interactions among anxiety diagnosis, maternal care, and baseline cortisol on food intake in a new environment in humans. A community sample of 32 adolescents and young adults was evaluated for: psychiatric diagnosis using standardized interviews, maternal care using the Parental Bonding Inventory (PBI), caloric consumption in a new environment (meal choice at a snack bar), and salivary cortisol. They also performed a brain fMRI task including the visualization of palatable foods vs. neutral items. The study found a three-way interaction between anxiety diagnosis, maternal care, and baseline cortisol levels on the total calories consumed (snacks) in a new environment. This interaction means that for those with high maternal care, there were no significant associations between cortisol levels and food intake in a new environment. However, for those with low maternal care and who have an anxiety disorder (affected), cortisol was associated with higher food intake; whereas for those with low maternal care and who did not have an anxiety disorder (resilient), cortisol was negatively associated with lower food intake. In addition, higher anxiety symptoms were associated with decreased activation in the superior and middle frontal gyrus when visualizing palatable vs. neutral items in those reporting high maternal care. These results in humans mimic experimental research findings and demonstrate that a combination of anxiety diagnosis and maternal care moderate the relationship between the HPA axis functioning, anxiety, and feeding behavior in adolescents and young adults.

Intrauterine growth restriction increases the preference for palatable foods and affects sensitivity to food rewards in male and female adult rats.

Clinical evidence suggests that intrauterine growth restriction (IUGR) can cause persistent changes in the preference for palatable foods. In this study, we compared food preferences, the response to food rewards, and the role of the mesolimbic dopaminergic system in feeding behavior, between IUGR and control rats. Time-mated pregnant Sprague-Dawley rats were randomly allocated to a control group (standard chow ad libitum) or a 50% food restriction (FR) group, which received 50% of the control dams׳ habitual intake. These diets were provided from gestation day 10 to the 21st day of lactation. Within 24h of birth, pups were cross-fostered and divided into four groups: Adlib/Adlib, FR/Adlib, FR/FR, Adlib/FR. Standard chow consumption was compared between all groups. Food preferences, conditioned place preference to a palatable diet, and the levels of tyrosine hydroxylase (TH) phosphorylation and D2 receptors in the nucleus accumbens were analyzed and compared between the two groups of interest: Adlib/Adlib (control) and FR/Adlib (exposed to growth restriction during the fetal period only). IUGR adult rats had a stronger preference for palatable foods, but showed less conditioned place preference to a palatable diet than controls. D2 receptors levels were lower in IUGR rats. At baseline, TH and pTH levels were higher in FR/Adlib than control males. Measurements taken after exposure to sweet foods revealed higher levels of TH and pTH in FR/Adlib than control females. These data showed that IUGR rats exhibited a preference for palatable foods, potentially due to alterations in their mesolimbic reward pathway. Additionally, the changes observed in the mesolimbic dopaminergic system of IUGR rats proved to be sex-specific. This article is part of a Special Issue entitled 1618.

Both food restriction and high-fat diet during gestation induce low birth weight and altered physical activity in adult rat offspring: the "Similarities in the Inequalities" model.

We have previously described a theoretical model in humans, called "Similarities in the Inequalities", in which extremely unequal social backgrounds coexist in a complex scenario promoting similar health outcomes in adulthood. Based on the potential applicability of and to further explore the "similarities in the inequalities" phenomenon, this study used a rat model to investigate the effect of different nutritional backgrounds during gestation on the willingness of offspring to engage in physical activity in adulthood. Sprague-Dawley rats were time mated and randomly allocated to one of three dietary groups: Control (Adlib), receiving standard laboratory chow ad libitum; 50% food restricted (FR), receiving 50% of the ad libitum-fed dam's habitual intake; or high-fat diet (HF), receiving a diet containing 23% fat. The diets were provided from day 10 of pregnancy until weaning. Within 24 hours of birth, pups were cross-fostered to other dams, forming the following groups: Adlib_Adlib, FR_Adlib, and HF_Adlib. Maternal chow consumption and weight gain, and offspring birth weight, growth, physical activity (one week of free exercise in running wheels), abdominal adiposity and biochemical data were evaluated. Western blot was performed to assess D2 receptors in the dorsal striatum. The "similarities in the inequalities" effect was observed on birth weight (both FR and HF groups were smaller than the Adlib group at birth) and physical activity (both FR_Adlib and HF_Adlib groups were different from the Adlib_Adlib group, with less active males and more active females). Our findings contribute to the view that health inequalities in fetal life may program the health outcomes manifested in offspring adult life (such as altered physical activity and metabolic parameters), probably through different biological mechanisms.

Increased palatable food intake and response to food cues in intrauterine growth-restricted rats are related to tyrosine hydroxylase content in the orbitofrontal cortex and nucleus accumbens.

Intrauterine growth restriction (IUGR) is associated with altered food preferences, which may contribute to increased risk of obesity. We evaluated the effects of IUGR on attention to a palatable food cue, as well as tyrosine hydroxylase (TH) content in the orbitofrontal cortex (OFC) and nucleus accumbens (NAcc) in response to sweet food intake. From day 10 of gestation and through lactation, Sprague-Dawley rats received either an ad libitum (Adlib) or a 50% food-restricted (FR) diet. At birth, pups were cross-fostered, generating four groups (gestation/lactation): Adlib/Adlib (control), FR/Adlib (intrauterine growth-restricted), Adlib/FR, and FR/FR. Adult attention to palatable food cues was measured using the Attentional Set-Shifting Task (ASST), which uses a sweet pellet as reward. TH content in the OFC and NAcc was measured at baseline and in response to palatable food intake. At 90 days of age, FR/Adlib males ate more sweet food than controls, without differences in females. However, when compared to Controls, FR/Adlib females needed fewer trials to reach criterion in the ASST (p=0.04) and exhibited increased TH content in the OFC in response to sweet food (p=0.03). In the NAcc, there was a differential response of TH content after sweet food intake in both FR/Adlib males and females (p<0.05). Fetal programming of adult food preferences involves the central response to palatable food cues and intake, affecting dopamine release in select structures of the brain reward system.