Neural correlates of appetite in adolescents.

Appetitive characteristics are associated with child adiposity, but their biological underpinnings are unclear. We sought to investigate the neural correlates of psychometric and behavioral measures of appetitive characteristics in youth. Adolescents (14-18y; 39F, 37M) varying in familial obesity risk and body weight (20% with overweight, 24% with obesity) viewed pictures of high energy-density (ED) foods, low-ED foods and non-foods during fMRI scanning on two separate days. On one day participants consumed a 474 ml preload of water (0 kcal, fasted) and on another (counter-balanced) 474 ml milkshake (480 kcal, fed), before scanning. A multi-item ad libitum meal (ALM) followed scanning. Parents completed Child Eating Behavior Questionnaire (CEBQ) sub-scales assessing food approach and food self-regulation. Caloric compensation was calculated as the percentage of preload intake compensated for by down-regulation of ALM intake in the fed vs. fasted condition. Analyses correcting for multiple comparisons demonstrated that, for the fasted condition, higher CEBQ Food Responsiveness scores were associated with greater activation to high-ED (vs. low-ED) foods in regions implicated in food reward (insula, rolandic operculum, putamen). In addition, higher caloric compensation was associated with greater fed vs. fasted activations in response to foods (vs. non-foods) in thalamus and supramarginal gyrus. Uncorrected analyses provided further support for associations of different measures of appetitive characteristics with brain responses to food cues in each condition. Measures of appetitive characteristics demonstrated overlapping and distinct associations with patterns of brain activation elicited by food cues in fasted and fed states. Understanding the neural basis of appetitive characteristics could aid development of biobehaviorally-informed obesity interventions.

Behavioural susceptibility theory: the role of appetite in genetic susceptibility to obesity in early life.

Excess weight gained during the early years and, in particular, rapid weight gain in the first 2 years of life, are a major risk factors for adult obesity. The growing consensus is that childhood obesity develops from a complex interaction between genetic susceptibility and exposure to an 'obesogenic' environment. Behavioural susceptibility theory (BST) was developed to explain the nature of this gene-environment interaction, and why the 'obesogenic' environment does not affect all children equally. It hypothesizes that inherited variation in appetite, which is present from birth, determines why some infants and children overeat, and others do not, in response to environmental opportunity. That is, those who inherit genetic variants promoting an avid appetite are vulnerable to overeating and developing obesity, while those who are genetically predisposed to have a smaller appetite and lower interest in food are protected from obesity-or even at risk of being underweight. We review the breadth of research to-date that has contributed to the evidence base for BST, focusing on early life, and discuss implications and future directions for research and theory. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part I)'.

Parental stress, food parenting practices and child snack intake during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented disruptions to the lives of families. This study aimed to investigate the impact of pandemic-associated stress on food parenting practices including interactions surrounding snacks, and child diet. METHODS: Parents (N = 318) of 2-12-year old children completed a cross-sectional online survey assessing current COVID-19-specific stress, pre-COVID-19 stress, financial stress (e.g. food insecurity), food parenting practices, and child snack intake frequency. Structural Equation Modeling was used to model simultaneous paths of relationships and test direct and indirect effects. RESULTS: Stress, including financial hardship, was higher compared with before the crisis. The majority of children had regular mealtimes and irregular snack times. Higher COVID-19-specific stress was associated with more non-nutritive use of food and snacks (e.g. emotional and instrumental feeding), but also more structure and positive interactions (e.g. eating with or engaging with child around mealtimes). Higher COVID-19-specific stress was also associated with greater child intake frequency of sweet and savory snacks, with some evidence for mediation by snack parenting practices. CONCLUSION: Our findings indicate that stress associated with the COVID-19 pandemic may be linked to child snack intake with potential impacts on child obesity risk, and suggest several modifiable points of intervention within the family context.

Effect of Age on GABA+ and Glutathione in a Pediatric Sample.

BACKGROUND AND PURPOSE: Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the human brain and is implicated in several neuropathologies. Glutathione is a major antioxidant in the brain and is considered a marker of oxidative stress. Several studies have reported age-related declines in GABA levels in adulthood, but the trajectory of both GABA and glutathione during childhood has not been well explored. The aim of this study is to establish how GABA and glutathione vary with age during early development. MATERIALS AND METHODS: Twenty-three healthy children (5.6-13.9 years of age) were recruited for this study. MR imaging/MR spectroscopy experiments were conducted on a 3T MR scanner. A 27-mL MR spectroscopy voxel was positioned in the frontal lobe. J-difference edited MR spectroscopy was used to spectrally edit GABA and glutathione. Data were analyzed using the Gannet software, and GABA+ (GABA + macromolecules/homocarnosine) and glutathione were quantified using water (GABA+H2O and GlutathioneH2O) and Cr (GABA+/Cr and glutathione/Cr) as concentration references. Also, the relative gray matter contribution to the voxel volume (GMratio) was estimated from structural images. Pearson correlation coefficients were used to examine the association between age and GABA+H2O (and glutathioneH2O), between age and GABA+/Cr (and glutathione/Cr), and between age and GMratio. RESULTS: Both GABA+H2O (r = 0.63, P = .002) and GABA+/Cr (r = 0.48, P = .026) significantly correlated with age, whereas glutathione measurements and GMratio did not. CONCLUSIONS: We demonstrate increases in GABA and no differences in glutathione with age in a healthy pediatric sample. This study provides insight into neuronal maturation in children and may facilitate better understanding of normative behavioral development and the pathophysiology of developmental disorders.

Morning and afternoon appetite and gut hormone responses to meal and stress challenges in obese individuals with and without binge eating disorder.

BACKGROUND: Eating late in the day is common, and stress can induce eating. Little is understood about how time of day and stress interact to affect appetite and thereby body weight. These may be particularly important influences in binge eaters, who tend to binge in the evening, and in response to stress. METHOD: Obese participants with (n=16) and without (n=16) binge eating disorder (BED) participated in two identical test protocols beginning either in the morning or the afternoon (AM condition/PM condition), each following an 8 h fast. For each protocol, they first received a standardized liquid meal (0900/1600 hours), then a stress test (Socially Evaluated Cold Pressor Test, 1110/1810 hours), and then a multi-item ad libitum buffet meal (1140/1840 hours) while rating appetite and stress and having blood drawn for hormone measures. RESULTS: Appetite at baseline was greater in the PM than in the AM condition (higher hunger, lower fullness). Following the liquid meal, area under the curve (AUC) values for hunger and ghrelin were greater and AUC values for peptide YY lower in the PM than in the AM condition. Only those with BED showed lower fullness AUC in the PM condition, as well as a pattern of higher initial PM and lower initial AM ghrelin. Following the stress test, cortisol and ghrelin increased in both the AM and PM conditions, but higher ghrelin AUC and lower cortisol AUC were observed in the PM condition. Again, only participants with BED showed lower fullness AUC in the PM condition. Buffet meal intake was similar across groups and conditions but those with BED reported greater loss of control and binge resemblance than those without. CONCLUSIONS: Afternoon/evening may be a high-risk period for overeating, particularly when paired with stress exposure, and for those with binge eating.

Caloric compensation in preschool children: Relationships with body mass and differences by food category.

Maintaining a healthy weight may involve compensating for previously consumed calories at subsequent meals. To test whether heavier children demonstrated poorer caloric compensation across a range of conditions, and to explore whether compensation failure was the result of inadequate adjustment of overall intake or specific over-consumption of highly palatable, high energy-density 'junk' foods, we administered two compensation tests to a sample of 4-5 y olds. For Test A, preloads varied only in carbohydrate content and were organoleptically indistinguishable (200 ml orange-flavored beverage [0 kcal vs. 200 kcal]). For Test B, the preloads varied substantially in both macronutrient composition and learned gustatory cues to caloric content (200 ml water [0 kcal] vs. 200 ml strawberry milkshake [200 kcal]). Each preload was followed 30 min later by a multi-item ad-libitum meal containing junk foods (chocolate cookies, cheese-flavored crackers) and core foods (fruits and vegetables, bread rolls, protein foods). Testing took place at the children's own school under normal lunch-time conditions. Children were weighed and measured. Caloric compensation occurred in both tests, in terms of total, junk and core food intake (RMANOVA, all p < 0.01). Higher BMI z scores were associated with greater average caloric compensation (r = -0.26; p < 0.05), such that overweight/obese children showed least compensation (41%), children over the 50th centile the next least (59%), and children under the 50th centile (80%) the most. For Test A only, obese/overweight children compensated less well than normal-weight children in terms of junk food intake (RMANOVA preload-by-weight group interaction p < 0.05), with no significant effect for core foods. Our results suggest that caloric compensation is consistently poorer in heavier children, and that overweight/obese children's preferences for junk foods may overwhelm intake regulation mechanisms within meals containing those foods.

Lunch-time food choices in preschoolers: Relationships between absolute and relative intakes of different food categories, and appetitive characteristics and weight.

Children's appetitive characteristics measured by parent-report questionnaires are reliably associated with body weight, as well as behavioral tests of appetite, but relatively little is known about relationships with food choice. As part of a larger preloading study, we served 4-5year olds from primary school classes five school lunches at which they were presented with the same standardized multi-item meal. Parents completed Child Eating Behavior Questionnaire (CEBQ) sub-scales assessing satiety responsiveness (CEBQ-SR), food responsiveness (CEBQ-FR) and enjoyment of food (CEBQ-EF), and children were weighed and measured. Despite differing preload conditions, children showed remarkable consistency of intake patterns across all five meals with day-to-day intra-class correlations in absolute and percentage intake of each food category ranging from 0.78 to 0.91. Higher CEBQ-SR was associated with lower mean intake of all food categories across all five meals, with the weakest association apparent for snack foods. Higher CEBQ-FR was associated with higher intake of white bread and fruits and vegetables, and higher CEBQ-EF was associated with greater intake of all categories, with the strongest association apparent for white bread. Analyses of intake of each food group as a percentage of total intake, treated here as an index of the child's choice to consume relatively more or relatively less of each different food category when composing their total lunch-time meal, further suggested that children who were higher in CEBQ-SR ate relatively more snack foods and relatively less fruits and vegetables, while children with higher CEBQ-EF ate relatively less snack foods and relatively more white bread. Higher absolute intakes of white bread and snack foods were associated with higher BMI z score. CEBQ sub-scale associations with food intake variables were largely unchanged by controlling for daily metabolic needs. However, descriptive comparisons of lunch intakes with expected amounts based on metabolic needs suggested that overweight/obese boys were at particularly high risk of overeating. Parents' reports of children's appetitive characteristics on the CEBQ are associated with differential patterns of food choice as indexed by absolute and relative intake of various food categories assessed on multiple occasions in a naturalistic, school-based setting, without parents present.

Pseudomonas aeruginosa Induced Airway Epithelial Injury Drives Fibroblast Activation: A Mechanism in Chronic Lung Allograft Dysfunction.

Bacterial infections after lung transplantation cause airway epithelial injury and are associated with an increased risk of developing bronchiolitis obliterans syndrome. The damaged epithelium is a source of alarmins that activate the innate immune system, yet their ability to activate fibroblasts in the development of bronchiolitis obliterans syndrome has not been evaluated. Two epithelial alarmins were measured longitudinally in bronchoalveolar lavages from lung transplant recipients who developed bronchiolitis obliterans syndrome and were compared to stable controls. In addition, conditioned media from human airway epithelial cells infected with Pseudomonas aeruginosa was applied to lung fibroblasts and inflammatory responses were determined. Interleukin-1 alpha (IL-1α) was increased in bronchoalveolar lavage of lung transplant recipients growing P. aeruginosa (11.5 [5.4-21.8] vs. 2.8 [0.9-9.4] pg/mL, p < 0.01) and was significantly elevated within 3 months of developing bronchiolitis obliterans syndrome (8.3 [1.4-25.1] vs. 3.6 [0.6-17.1] pg/mL, p < 0.01), whereas high mobility group protein B1 remained unchanged. IL-1α positively correlated with elevated bronchoalveolar lavage IL-8 levels (r(2)  = 0.6095, p < 0.0001) and neutrophil percentage (r(2)  = 0.25, p = 0.01). Conditioned media from P. aeruginosa infected epithelial cells induced a potent pro-inflammatory phenotype in fibroblasts via an IL-1α/IL-1R-dependent signaling pathway. In conclusion, we propose that IL-1α may be a novel therapeutic target to limit Pseudomonas associated allograft injury after lung transplantation.

Cortisol and ghrelin concentrations following a cold pressor stress test in overweight individuals with and without night eating.

OBJECTIVE: To explore appetite-related hormones following stress in overweight individuals, and their relationship with night eating (NE) status. METHOD: We measured plasma cortisol and ghrelin concentrations, and recorded ratings of stress and hunger in response to a physiological laboratory stressor (cold pressor test, CPT), in overweight women with (n=11; NE) and without (n=17; non-NE) NE. RESULTS: Following the CPT, cortisol (P<0.001) and ghrelin (P<0.05) levels increased, as did stress and hunger ratings (all P<0.001), across all subjects (NE and non-NE). NE exhibited higher baseline cortisol (P<0.05) levels than non-NE. NE also had greater cortisol area under the curve (AUC) than non-NE (P=0.019), but not when controlling for baseline cortisol levels. Ghrelin baseline and AUC did not differ between groups. NE showed higher AUC stress (P<0.05), even when controlling for baseline stress. DISCUSSION: Overweight individuals showed increased cortisol, ghrelin, stress and hunger following a laboratory stressor, and there was some evidence for greater increases in cortisol and subjective stress among NE. The greater AUC cortisol level in NE was due to higher baseline levels, but the group difference in stress was in direct response to the stressor. Our results support a role for cortisol and stress in NE.

Neuroimaging and obesity: current knowledge and future directions.

Neuroimaging is becoming increasingly common in obesity research as investigators try to understand the neurological underpinnings of appetite and body weight in humans. Positron emission tomography (PET), functional magnetic resonance imaging (fMRI) and magnetic resonance imaging (MRI) studies examining responses to food intake and food cues, dopamine function and brain volume in lean vs. obese individuals are now beginning to coalesce in identifying irregularities in a range of regions implicated in reward (e.g. striatum, orbitofrontal cortex, insula), emotion and memory (e.g. amygdala, hippocampus), homeostatic regulation of intake (e.g. hypothalamus), sensory and motor processing (e.g. insula, precentral gyrus), and cognitive control and attention (e.g. prefrontal cortex, cingulate). Studies of weight change in children and adolescents, and those at high genetic risk for obesity, promise to illuminate causal processes. Studies examining specific eating behaviours (e.g. external eating, emotional eating, dietary restraint) are teaching us about the distinct neural networks that drive components of appetite, and contribute to the phenotype of body weight. Finally, innovative investigations of appetite-related hormones, including studies of abnormalities (e.g. leptin deficiency) and interventions (e.g. leptin replacement, bariatric surgery), are shedding light on the interactive relationship between gut and brain. The dynamic distributed vulnerability model of eating behaviour in obesity that we propose has scientific and practical implications.

Parental feeding behaviours and motivations. A qualitative study in mothers of UK pre-schoolers.

Parental feeding behaviours are considered major influences on children's eating behaviour. However, many questionnaire studies of feeding neglect subtle distinctions between specific feeding strategies and practices in favour of eliciting general feeding goals, and do not take account of the context provided by parents' motivations. These factors may be critical to understanding child outcomes and engaging parents in child obesity prevention. The present study obtained interview and diary data on specific feeding behaviours and underlying motivations from 22 mothers of predominantly healthy weight 3-5 y olds in the UK. Parents described a wide range of efforts to promote or restrict intake that were largely motivated by practical and health considerations and only rarely by concern about weight. There was also evidence for instrumental feeding, rules surrounding meal-time, child involvement, and parental flexibility in relation to feeding. Almost all parents described responding to children's appetitive traits, consistent with growing evidence for genetically influenced individual differences in children's appetite. These findings suggest that in order to engage parents of currently healthy weight children, obesity prevention advice should aim to satisfy their primary motivations (practicality, health), and be framed as helping parents to respond sensitively and appropriately to different children's characteristics.

Neuroimaging, gut peptides and obesity: novel studies of the neurobiology of appetite.

Two major biological players in the regulation of body weight are the gut and the brain. Peptides released from the gut convey information about energy needs to areas of the brain involved in homeostatic control of food intake. There is emerging evidence that human food intake is also under the control of cortical and subcortical areas related to reward and cognition. The extent to which gut hormones influence these brain areas is not fully understood. Novel methods combining the study of neural activity and hormonal signalling promise to advance our understanding of gut-brain interactions. Here, we review a growing number of animal and human studies using neuroimaging methods (functional magnetic resonance imaging, positron emission tomography) to measure brain activation in relation to nutrient loads and infusion of gut peptides. Implications for current and future pharmacological treatments for obesity are discussed.

Associations between child weight and maternal feeding styles are mediated by maternal perceptions and concerns.

OBJECTIVE: To determine whether controlling parental feeding practices are associated with children's adiposity and test the hypothesis that any associations are mediated by maternal perception of their child's weight. METHOD: Children aged 7-9 years (n=405) were weighed and measured at school as part of the Physical Exercise and Appetite in CHildren Study (PEACHES). Adiposity was indexed with body mass index s.d. scores. The Child Feeding Questionnaire was completed by 53% of mothers of participating children (n=213). Mothers reported whether they thought their child was overweight, normal weight or underweight, and rated their concern about future overweight on a 5-point scale. RESULTS: Higher child adiposity was associated with lower 'pressure to eat' and higher 'restriction' scores. Restriction increased linearly with maternal concern about overweight, and maternal concern about overweight fully mediated the association between child adiposity and restriction. Use of pressure increased as mothers perceived their child to be thinner, but perceived weight did not mediate the association between child weight status and maternal pressure to eat. Monitoring was not associated with child adiposity, maternal perception of weight or concern about overweight. CONCLUSION: Restriction appears to be a consequence of mothers' concern about their child becoming overweight rather than a cause of children's weight gain. Pressure may be a more complex response that is influenced by the desire to encourage consumption of healthy foods as well as ensure adequate energy intake and appropriate weight gain.

Genetic influence on appetite in children.

BACKGROUND: The modern environment is ubiquitously 'obesogenic', yet people vary enormously in weight. One factor contributing to weight variation could be genetically determined differences in appetite that modulate susceptibility to the environment. We assessed the relative contribution of genes and environment for two aspects of appetite that have been implicated in obesity. METHODS: Parents of a population-based sample of 8- to 11-year-old twins (n=5435 pairs) completed validated, questionnaire measures of responsiveness to satiety and responsiveness to food cues for both children. RESULTS: Quantitative genetic model fitting gave estimates of 63% (95% confidence interval: 39-81%) for the heritability of satiety responsiveness and 75% (52-85%) for food cue responsiveness. Shared and non-shared environmental influences were 21% (0-51%) and 16% (10-21%) for satiety responsiveness, and 10% (0-38%) and 15% (10-18%) for food cue responsiveness, respectively. CONCLUSIONS: The high heritability of appetitive traits that are known to be related to weight suggests that genetic vulnerability to weight gain could operate through behavioural as well as metabolic pathways. Intervention strategies aimed at improving satiety responsiveness and reducing food cue responsiveness in high-risk individuals could help in preventing the development of obesity.

Adiposity and 'eating in the absence of hunger' in children.

OBJECTIVE: To examine the association between eating in the absence of hunger (EAH) and adiposity in children. DESIGN: Two cross-sectional studies in community settings. SUBJECTS: For study 1, 348 children (178 girls and 170 boys) aged 7-9 years were recruited as part of the Physical Exercise and Appetite in Children Study. In study 2, participants were a subsample of children aged 9-12 years (N=316; 192 girls and 124 boys) from the Twins Early Development Study. MEASUREMENTS: EAH was operationalized as intake of highly palatable sweet snacks after a mixed meal at school (study 1) or home (study 2). Weight (kg) and height (m) measurements were used to calculate the body mass index (BMI) s.d. scores. Children were grouped using the standard criteria for underweight, healthy weight, overweight and obesity. The healthy weight range was further subdivided into lower healthy weight (50th centile) to examine the distribution of EAH across the adiposity continuum. RESULTS: In both studies, EAH showed a significant positive association with adiposity in boys after adjusting for covariates (P<0.001), with a linear increase in the intake across underweight, healthy weight and overweight groups. The association between EAH and adiposity was not significant in girls in either study, although in study 1, results showed a quadratic trend, with EAH increasing through the underweight and healthy weight ranges and decreasing in overweight and obese groups. CONCLUSION: EAH is a behavioural phenotype that is not specific to overweight children but instead shows a graded association with adiposity across the weight continuum, particularly in boys. In this study, the effect was less pronounced in girls, which may reflect social desirability pressures constraining food intake among heavier girls.

Continuity and stability of eating behaviour traits in children.

OBJECTIVE: To discover whether eating behaviour traits show continuity and stability over childhood. SUBJECTS/METHODS: Mothers of 428 twin children from the Twins Early Development Study participated in a study of eating and weight in 1999 when the children were 4 years old. Families were contacted again in 2006 when the children were aged 10 years, with complete data on 322 children; a response rate of 75%. At both times, mothers completed the Child Eating Behaviour Questionnaire (CEBQ) for each child. Continuity was assessed with correlations between scores at the two time points, and stability by changes in mean scores over time. RESULTS: For all CEBQ subscales, correlations between the two time points were highly significant (P-values <0.001). For satiety responsiveness, slowness in eating, food responsiveness, enjoyment of food, emotional overeating and food fussiness, correlations ranged from r=0.44 to 0.55, with lower continuity for emotional undereating (r=0.29). Over time, satiety responsiveness, slowness in eating, food fussiness, and emotional undereating decreased, while food responsiveness, enjoyment of food and emotional overeating increased. CONCLUSIONS: Eating behaviours, including those associated with a tendency to overeat, emerge early in the developmental pathway and show levels of individual continuity comparable to stable personality traits. Appetitive traits related to higher satiety tended to decrease with maturation, while those associated with food responsiveness tended to increase. This pattern is consistent with strong tracking of body mass index alongside a progressive increase in the risk of obesity.

Parental perceptions of overweight in 3-5 y olds.

OBJECTIVE: To assess the accuracy of parents' perceptions of their 3 to 5 y old children's weight status in a large UK sample. METHOD: Parental perception and concern about child weight, demographic variables, and children's height and weight were obtained for 564 parent-child dyads. RESULTS: Only 1.9% of parents of overweight children and 17.1% of parents of obese children described their child as overweight. The odds of parents perceiving the child as overweight were increased for overweight (2.7; 95% CI 0.4, 16.5) and obese (28.5; 7.1, 115.4) compared with normal weight children, but were not associated with parental weight or with any demographic factors. Although few parents perceived their overweight children as overweight, more (66.2%) expressed concern about their overweight child becoming overweight in the future. Odds of concern were progressively higher for overweight (2.5; 1.6, 3.9) and obese children (4.6; 2.2, 9.7), and were also higher for parents who were themselves overweight (1.9; 1.2, 2.9) or obese (2.5; 1.3, 4.8). CONCLUSION: These findings suggest that parents of 3-5 y olds show poor awareness of their child's current weight status. Reframing discussions in terms of preventing future overweight may be an effective way to engage parents.