Susan Carnell

Obesity associated genetic variation in FTO is associated with diminished satiety.

CONTEXT Polymorphisms within the FTO gene have consistently been associated with obesity across multiple populations. However, to date, it is not known whether the association between genetic variation in FTO and obesity is mediated through effects on energy intake or energy expenditure. OBJECTIVE Our objective was to examine the association between alleles of FTO known to increase obesity risk and measures of habitual appetitive behavior. METHODS The intronic FTO single nucleotide polymorphism (rs9939609) was genotyped in 3337 United Kingdom children in whom measures of habitual appetitive behavior had been assessed using two scales (Satiety Responsiveness and Enjoyment of Food) from the Child Eating Behaviour Questionnaire, a psychometric tool that has been validated against objective measures of food intake. Associations of FTO genotype with indices of adiposity and appetite were assessed by ANOVA. RESULTS As expected, the A allele was associated with increased adiposity in this cohort and in an independent case-control replication study of United Kingdom children of similar age. AA homozygotes had significantly reduced Satiety Responsiveness scores (P = 0.008, ANOVA). Mediation analysis indicated that the association of the AA genotype with increased adiposity was explained in part through effects on Satiety Responsiveness. CONCLUSIONS We have used a unique dataset to examine the relationship between a validated measure of childrens habitual appetitive behavior and FTO obesity risk genotype and conclude that the commonest known risk allele for obesity is likely to exert at least some of its effects by influencing appetite.

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.

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.

Food neophobia and mealtime food consumption in 4-5 year old children.

BackgroundPrevious research has documented a negative association between maternal report of child food neophobia and reported frequency of consumption of fruit, vegetables, and meat. This study aimed to establish whether neophobia is associated with lower intake of these food types in naturalistic mealtime situations.MethodsOne hundred and nine parents of 4–5 year olds completed questionnaires which included a six-item version of the Child Food Neophobia Scale (CFNS). The children took part in a series of 3 test lunch meals at weekly intervals at school at which they were presented with: chicken, cheese, bread, cheese crackers, chocolate biscuits, grapes and tomatoes or carrot sticks. Food items served to each child were weighed before and after the meal to assess total intake of items in four categories: Fruit and vegetables, Protein foods, Starchy foods and Snack foods. Pearson Product Moment Correlations and independent t tests were performed to examine associations between scores on the CFNS and consumption during lunches.ResultsNeophobia was associated with lower consumption of fruit and vegetables, protein foods and total calories, but there was no association with intake of starch or snack foods.ConclusionThese results support previous research that has suggested that neophobia impacts differentially on consumption of different food types. Specifically it appears that children who score highly on the CFNS eat less fruit, vegetables and protein foods than their less neophobic peers. Attempts to increase intake of fruit, vegetables and protein might usefully incorporate strategies known to reduce the neophobic response.

Selective Reduction in Neural Responses to High Calorie Foods Following Gastric Bypass Surgery

Objective:To investigate changes in neural activation and desire to eat in response to appetitive cues from pre- to postbariatric surgery for obesity. Background:Roux-en-Y gastric bypass (RYGB) is the most common bariatric procedure. However, the mechanisms of action in RYGB are not well understood. A significant proportion of the resulting reduction in caloric intake is unaccounted for by the restrictive and malabsorptive mechanisms and is thought to be mediated by neuroendocrine function. Numerous investigations of postsurgical changes in gut peptides have resulted; however, changes in neural activation after RYGB surgery have not been previously investigated. METHODS:Functional magnetic resonance imaging and verbal rating scales were used to assess brain activation and desire to eat in response to high- and low-calorie food cues in 10 female patients 1-month pre- and post-RYGB surgery. Results:Postsurgical reductions in brain activation were found in key areas within the mesolimbic reward pathway, which were significantly more pronounced in response to food cues that were high (vs. low) in caloric density. These changes mirrored concurrent postsurgical reductions in desire to eat, which were also greater in response to food cues that were high versus low in caloric density (P = 0.007). Conclusions:Findings support the contention that RYGB surgery leads to substantial changes in neural responses to food cues encountered in the environment, provide a potential mechanism for the selective reduction in preferences for high-calorie foods, and suggest partial neural mediation of changes in caloric intake seen after RYGB surgery.

Increasing heritability of BMI and stronger associations with the FTO gene over childhood.

The growing evidence of health risks associated with the rise in childhood obesity adds to the urgency of understanding the determinants of BMI. Twin analyses on repeated assessments of BMI in a longitudinal sample of >7,000 children indicated that the genetic influence on BMI becomes progressively stronger, with heritability increasing from 0.48 at age 4 to 0.78 at age 11. In the same large twin sample, the association between a common variant in the FTO gene and BMI increased in parallel with the rise in heritability, going from R2 < 0.001 at age 4 to R2 = 0.01 at age 11. These findings suggest that expression of FTO may become stronger throughout childhood. Increases in heritability may also be due to children increasingly selecting environments correlated with their genetic propensities.

Eating rate is a heritable phenotype related to weight in children

BACKGROUND There is growing interest in the heritability of behavioral phenotypes related to adiposity. One potential candidate is the speed of eating, although existing evidence for an association with weight is mixed. OBJECTIVE We aimed to assess the speed of eating in a sample of 10-12-y-old children to test the hypotheses that higher eating rate is related to greater adiposity and that eating rate is a heritable characteristic. DESIGN Video data of 254 twin children eating a standard meal at home were used to record eating rate (bites/min) and changes in eating rate across the 4 quarters of the meal. Adiposity was indexed with body mass index SD scores relative to British 1990 norms; for some analyses, children were categorized into groups of overweight or obese and into 2 subgroups of normal-weight (lower normal-weight or higher normal-weight) for comparison of the eating rate within the normal range as well as between clinical and nonclinical groups. All analyses controlled for clustering in twin pairs. Heritability of eating rate was modeled by using standard twin methods. RESULTS There was a significant linear association across the 3 weight groups for eating rate (P = 0.010), and regression analyses showed that eating rate increased by 0.18 bites/min for each 1-unit increase in body mass index SD score (P = 0.005). The heritability of eating rate was high (0.62; 95% CI: 0.45, 0.74). There was no association between weight group and a change (ie, deceleration) in eating rate over the mealtime. CONCLUSION Faster eating appears to be a heritable behavioral phenotype related to higher weight.

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.

Associations between Multiple Measures of Parental Feeding and Children's Adiposity in United Kingdom Preschoolers

Objective: Research into the association between parental control over feeding and childrens adiposity has produced inconclusive results. Some studies have found parental control to be associated with unhealthy food choices and disordered intake regulation, whereas others have found favorable or null associations between control and adiposity. This study hypothesized that variability in measures of parental feeding could contribute to these discrepancies. Scales from a range of existing parental feeding questionnaires were used together, in the same large sample of children, to examine associations with adiposity.

Development of Overweight in Children in Relation to Parental Weight and Socioeconomic Status

The purpose of the study was to test the hypothesis that socioeconomic status (SES) moderates the association between parental weight and changes in BMI from childhood to early adolescence. Participants included 428 twin children from 100 families with obese parents (“obese families”) and 114 sociodemographically matched families with normal‐weight parents (“lean families”) who were assessed in their homes (age = 4.4). Follow‐up study was conducted 7 years later (age = 11.2) on 346 children (81%). Complete data were available for 333 children. Family SES was indexed with maternal education. Childrens weights and heights were measured to calculate BMI s.d. scores based on 1990 British norms. Overweight was defined as >91st BMI centile. In children with obese parents, BMI s.d. scores increased from 0.51 at age 4 to 1.06 at age 11. In children with lean parents, BMI s.d. scores decreased from 0.11 to 0.05. Prevalence of overweight remained stable from age 4 to 11 in children with lean parents (8% to 9%), but it more than doubled in children with obese parents (17% to 45%). There was a significant interaction between parental weight and family SES (P < 0.01), so that in children with lean parents there was no SES difference in the BMI status from age 4 to 11; however, in children with obese parents, the increase in adiposity was significantly greater in lower SES families. These results suggest that parental leanness confers significant protection against development of overweight in children regardless of family SES, while parental obesity is an adverse prognostic sign, especially in lower SES families.