Relation of preconception eating behaviours to dietary pattern trajectories and gestational weight gain from preconception to late pregnancy.

Studies examining preconception eating behaviours with longitudinal dietary patterns from preconception to late pregnancy as well as gestational weight gain (GWG) are limited. We derived dietary pattern trajectories from preconception to late-pregnancy, and related preconception eating behaviours to these trajectories and GWG. Preconception eating behaviours were assessed using the Three-Factor Eating Questionnaire measuring cognitive restraint (CR) - conscious restriction of food intake, emotional eating (EE) - overeating in response to negative emotions, and uncontrolled eating (UE) - overeating with a feeling of lack of control. Dietary intakes were measured at preconception, 20-21 and 34-36 weeks' gestation with food frequency questionnaires. Dietary patterns were determined using factor analysis, and trajectories derived using group-based trajectory modelling. Inadequate and excessive GWG were defined according to Institute of Medicine guidelines based on weights at preconception and the last antenatal visit (median: 38 weeks' gestation). Two dietary patterns were derived: 'Fast Food, Fried Snacks and Desserts (FFD)' and 'Soup, Fish and Vegetables (SFV)'. Adherence trajectories from preconception to late-pregnancy were characterised as consistently high ("stable-high") and low ("stable-low"). Women with higher UE scores had higher odds of being in the "stable-high" trajectory (n = 34) of the FFD pattern [Odds Ratio (OR): 1.25, 95% Confidence Interval (CI): 1.03, 1.51], compared to "stable-low" (n = 260). Percentages of women with inadequate, adequate or excessive GWG were 21.7% (n = 70), 25.8% (n = 83), and 52.5% (n = 169), respectively; women with higher EE scores had a higher likelihood of excessive GWG [Relative Risk Ratio (RRR): 1.35, 95% CI: 1.02, 1.80], but this association was attenuated after adjusting for preconception body mass index. Eating behaviour interventions to improve dietary patterns among pregnant women may need to start as early as preconception, incorporating strategies to manage UE.

Conditioned overconsumption is dependent on reinforcer type in lean, but not obese, mice.

Associative learning can drive many different types of behaviors, including food consumption. Previous studies have shown that cues paired with food delivery while mice are hungry will lead to increased consumption in the presence of those cues at later times. We previously showed that overconsumption can be driven in male mice by contextual cues, using chow pellets. Here we extended our findings by examining other parameters that may influence the outcome of context-conditioned overconsumption training. We found that the task worked equally well in males and females, and that palatable substances such as high-fat diet and Ensure chocolate milkshake supported learning and induced overconsumption. Surprisingly, mice did not overconsume when sucrose was used as the reinforcer during training, suggesting that nutritional content is a critical factor. Interestingly, we also observed that diet-induced obese mice did not learn the task. Overall, we find that context-conditioned overconsumption can be studied in lean male and female mice, and with multiple reinforcer types.

Examining parents' experiences and challenges of feeding preschool children with avid eating behaviour.

Avid eating behaviours, including greater responsiveness to food cues and emotional over-eating, have been linked to child overweight and obesity. Parental feeding practices are modifiable components of a child's food environment and may be key levers for behaviour change in tailored interventions to support parents of children with avid eating behaviour. However, there is a lack of research examining parents' experiences in this context. This study aimed to explore parents' experiences of feeding children with avid eating behaviour and to understand any challenges experienced in this context. Semi-structured interviews with parents (N = 15) of a preschool child (3-5 years) identified as having an avid eating behaviour profile explored how children's avid eating manifests, the parental feeding practices used to manage avid eating, and the perceived effectiveness of these strategies. Data were analysed using reflexive thematic analysis. Four core themes were generated. Theme one, 'Have they got worms? Children's insatiable hunger', captures parents' interpretation of the complex ways in which avid eating behaviour manifests. Theme two, 'Parenthood as a duty', illustrates how parents' perceived responsibilities shape their feeding practices. Theme three, 'Lifelong habits', captures parents' use of responsive feeding practices to support children's healthy relationship with food. Theme four, 'Picking battles', captures the structure- and coercive-based feeding strategies commonly used to manage children's avid eating. This novel study provides an in-depth understanding of the complex ways that children's avid eating behaviour manifests, and the strategic and creative parental feeding practices used to manage these behaviours. Such findings are valuable for informing the development of future support resources for parents/caregivers to help their children with avid eating behaviours to develop a healthy relationship with food.

Specificity of Early Childhood Hyperphagia Profiles in Neurogenetic Conditions.

Hyperphagia is highly penetrant in Prader-Willi syndrome (PWS) and has increasingly been reported in other neurogenetic conditions (NGC). The Hyperphagia Questionnaire (HQ) was completed by caregivers of 4-8-year-olds with PWS (n = 17), Angelman syndrome (AS; n = 22), Williams syndrome (WS; n = 25), or low-risk controls (LRC; n = 35). All NGC groups were significantly elevated in HQ Total and Behavior scores compared to LRC. Only AS and WS were significantly elevated in the Drive domain, and only PWS in the Severity domain. After controlling for externalizing behavior, HQ Total scores were higher for PWS relative to other groups. Hyperphagic symptoms may not differentiate PWS from other NGCs in early childhood. However, hyperphagic phenotypes may be most severe in PWS. Further investigation of these profiles may inform etiology and syndrome-specific treatments.

Behavioral changes in patients with Prader-Willi syndrome receiving diazoxide choline extended-release tablets compared to the PATH for PWS natural history study.

BACKGROUND: Prader-Willi syndrome (PWS) is a rare neurobehavioral-metabolic disease caused by the lack of paternally expressed genes in the chromosome 15q11-q13 region, characterized by hypotonia, neurocognitive problems, behavioral difficulties, endocrinopathies, and hyperphagia resulting in severe obesity if energy intake is not controlled. Diazoxide choline extended-release (DCCR) tablets have previously been evaluated for their effects on hyperphagia and other behavioral complications of people with PWS in a Phase 3 placebo-controlled study of participants with PWS, age 4 and older with hyperphagia (C601) and in an open label extension study, C602. METHODS: To better understand the longer-term impact of DCCR, a cohort from PATH for PWS, a natural history study that enrolled participants with PWS age 5 and older, who met the C601 age, weight and baseline hyperphagia inclusion criteria and had 2 hyperphagia assessments ≥ 6 months apart, were compared to the C601/C602 cohort. Hyperphagia was measured using the Hyperphagia Questionnaire for Clinical Trials (HQ-CT, range 0-36). The primary analysis used observed values with no explicit imputation of missing data. A sensitivity analysis was conducted in which all missing HQ-CT assessments in the C601/C602 cohort were assigned the highest possible value (36), representing the worst-case scenario. Other behavioral changes were assessed using the Prader-Willi Syndrome Profile questionnaire (PWSP). RESULTS: Relative to the PATH for PWS natural history study cohort, the DCCR-treated C601/C602 cohort showed significant improvements in HQ-CT score at 26 weeks (LSmean [SE] -8.3 [0.75] vs. -2.5 [0.43], p < 0.001) and 52 weeks (LSmean [SE] -9.2 [0.77] vs. -3.4 [0.47], p < 0.001). The comparison between the cohorts remained significant in the worst-case imputation sensitivity analysis. There were also significant improvements in all domains of the PWSP at 26 weeks (all p < 0.001) and 52 weeks (all p ≤ 0.003) for C601/C602 participants compared to the PATH for PWS participants. CONCLUSION: Long-term administration of DCCR to people with PWS resulted in changes in hyperphagia and other behavioral complications of PWS that are distinct from the natural history of the syndrome as exemplified by the cohort from PATH for PWS. The combined effects of administration of DCCR should reduce the burden of the syndrome on the patient, caregivers and their families, and thereby may benefit people with PWS and their families. TRIAL REGISTRATION: Clinical study C601 was originally registered on ClinicalTrials.gov on February 22, 2018 (NCT03440814). Clinical study C602 was originally registered on ClinicalTrials.gov on October 22, 2018 (NCT03714373). PATH for PWS was originally registered on ClinicalTrials.gov on October 24, 2018 (NCT03718416).

The Tip of the Iceberg: Genotype of Puerto Rican Pediatric Obesity.

Childhood obesity is a significant public health concern, particularly among Hispanic populations. This study aimed to elucidate the genetic predisposition to obesity in Puerto Rican children of Hispanic descent, addressing a notable gap in existing research. A cohort of 103 children with obesity and hyperphagia underwent genetic screening for rare obesity-related variants. Clinical assessments and family history evaluations were conducted to characterize the demographic and clinical characteristics of the cohort. Genetic testing revealed a high prevalence of variants, with 73% of subjects having at least one reported variant. Pathogenic variants, predominantly associated with obesity-related ciliopathies, were identified in 7% of cases. Additionally, 90% of cases had variants of uncertain significance, highlighting the complexity of genetic contributions to obesity. This study emphasizes the critical need for further investigation into the genetic foundations of obesity, particularly within Hispanic communities. The findings emphasize the importance of early medical evaluation, vigilant monitoring for hyperphagia onset, and targeted interventions tailored to the unique genetic landscape of Puerto Rican children. This research provides a foundational framework for future studies to mitigate the impact of genetic obesity within this population.

Characterization of adults concerning the use of a hypothetical mHealth application addressing stress-overeating: an online survey.

BACKGROUND: About 40% of people respond to stress by consuming more unhealthy foods. This behavior is associated with increased energy intake and the risk of obesity. As mobile health (mHealth) applications (apps) have been shown to be an easy-to-use intervention tool, the characterization of potential app users is necessary to develop target group-specific apps and to increase adherence rates. METHODS: This cross-sectional online survey was conducted in the spring of 2021 in Germany. Sociodemographic data and data on personality (Big Five Inventory, BFI-10), stress-eating (Salzburg Stress Eating Scale, SSES), and technology behavior (Personal Innovativeness in the Domain of Information Technology, PIIT; Technology Acceptance Model 3, TAM 3) were collected. RESULTS: The analysis included 1228 participants (80.6% female, mean age: 31.4 ± 12.8 years, mean body mass index (BMI): 23.4 ± 4.3 kg/m2). Based on the TAM score, 33.3% (409/1228) of the participants had a high intention to use a hypothetical mHealth app to avoid stress-overeating. These persons are characterized by a higher BMI (24.02 ± 4.47 kg/m2, p < 0.001), by being stress-overeaters (217/409, 53.1%), by the personality trait "neuroticism" (p < 0.001), by having specific eating reasons (all p < 0.01), and by showing a higher willingness to adopt new technologies (p < 0.001). CONCLUSION: This study suggests that individuals who are prone to stress-overeating are highly interested in adopting an mHealth app as support. Participants with a high intention to use an mHealth app seem to have a general affinity towards new technology (PIIT) and appear to be more insecure with conflicting motives regarding their diet. TRIAL REGISTRATION: This survey was registered in the German Clinical Trials Register (Registration number: DRKS00023984).

IMPROVE 2022 International Meeting on Pathway-Related Obesity: Vision of Excellence.

Nearly 90 clinicians and researchers from around the world attended the first IMPROVE 2022 International Meeting on Pathway-Related Obesity. Delegates attended in person or online from across Europe, Argentina and Israel to hear the latest scientific and clinical developments in hyperphagia and severe, early-onset obesity, and set out a vision of excellence for the future for improving the diagnosis, treatment, and care of patients with melanocortin-4 receptor (MC4R) pathway-related obesity. The meeting co-chair Peter Kühnen, Charité Universitätsmedizin Berlin, Germany, indicated that change was needed with the rapidly increasing prevalence of obesity and the associated complications to improve the understanding of the underlying mechanisms and acknowledge that monogenic forms of obesity can play an important role, providing insights that can be applied to a wider group of patients with obesity. World-leading experts presented the latest research and led discussions on the underlying science of obesity, diagnosis (including clinical and genetic approaches such as the role of defective MC4R signalling), and emerging clinical data and research with targeted pharmacological approaches. The aim of the meeting was to agree on the questions that needed to be addressed in future research and to ensure that optimised diagnostic work-up was used with new genetic testing tools becoming available. This should aid the planning of new evidence-based treatment strategies for the future, as explained by co-chair Martin Wabitsch, Ulm University Medical Center, Germany.

Profiles of disordered eating behaviour in type 1 diabetes using the DEPS-R and behaviour and glycaemic outcomes in a real-life setting.

AIMS: The Diabetes Eating Problems Survey - Revised (DEPS-R) is commonly used to assess disordered eating behaviour (DEB) in individuals with type 1 diabetes and has advantages compared to other measures not specifically tailored to diabetes. A score ≥20 on the DEPS-R is used to indicate clinically significant DEB; however, it does not distinguish between eating disorder (ED) phenotypes necessary to guide treatment decisions, limiting clinical utility. METHODS: The current study used latent class analysis to identify distinct person-centred profiles of DEB in adults with type 1 diabetes using the DEPS-R. Analysis of Variance with Games Howell post-hoc comparisons was then conducted to examine the correspondence between the profiles and binge eating, insulin restriction and glycaemic control (HbA1c, mean blood glucose, and percent time spent in hyperglycaemia) during 3 days of assessment in a real-life setting. RESULTS: Latent class analysis indicated a 4-class solution, with patterns of item endorsement suggesting the following profiles: Bulimia, Binge Eating, Overeating and Low Pathology. Differences in binge eating, insulin restriction and glycaemic control were observed between profiles during 3 days of at-home assessment. The Bulimia profile was associated with highest HbA1c and 3-day mean blood glucose. CONCLUSIONS: There are common patterns of responses on the DEPS-R that appear to reflect different ED phenotypes. Profiles based on the DEPS-R corresponded with behaviour in the real-life setting as expected and were associated with different glycaemic outcomes. Results may have implications for the use of the DEPS-R in research and clinical settings.

Acquired hypothalamic obesity: A clinical overview and update.

Hypothalamic obesity (HO) is a rare and complex disorder that confers substantial morbidity and excess mortality. HO is a unique subtype of obesity characterized by impairment in the key brain pathways that regulate energy intake and expenditure, autonomic nervous system function, and peripheral hormonal signalling. HO often occurs in the context of hypothalamic syndrome, a constellation of symptoms that follow from disruption of hypothalamic functions, for example, temperature regulation, sleep-wake circadian control, and energy balance. Genetic forms of HO, including the monogenic obesity syndromes, often impact central leptin-melanocortin pathways. Acquired forms of HO occur as a result of tumours impacting the hypothalamus, such as craniopharyngioma, surgery or radiation to treat those tumours, or other forms of hypothalamic damage, such as brain injury impacting the region. Risk for severe obesity following hypothalamic injury is increased with larger extent of hypothalamic damage or lesions that contain the medial and posterior hypothalamic nuclei that support melanocortin signalling pathways. Structural damage in these hypothalamic nuclei often leads to hyperphagia, central insulin and leptin resistance, decreased sympathetic activity, low energy expenditure, and increased energy storage in adipose tissue, the collective effect of which is rapid weight gain. Individuals with hyperphagia are perpetually hungry. They do not experience fullness at the end of a meal, nor do they feel satiated after meals, leading them to consume larger and more frequent meals. To date, most efforts to treat HO have been disappointing and met with limited, if any, long-term success. However, new treatments based on the distinct pathophysiology of disturbed energy homeostasis in acquired HO may hold promise for the future.

Role of the intracerebroventricular injection of the visfatin and its interaction with neuropeptide Y and nitric systems on food intake in neonatal chicken.

Visfatin play an essential role in the central regulation of appetite in birds. This study aimed to determine role of intracerebroventricular (ICV) injection of the visfatin on food intake and its possible interaction with neuropeptide Y (NPY) and nitric oxide system in neonatal broiler chicken. In experiment 1, neonatal chicken received ICV injection visfatin (1, 2 and 4 µg). In experiment 2, chicken received ICV injection of B5063 (NPY1 receptor antagonist 1.25 µg), visfatin (4 µg) and co-injection of the B5063 + Visfatin. In experiments 3-6, SF22 (NPY2 receptor antagonist 1.25 µg), SML0891 (NPY5 receptor antagonist 1.25 µg), L-NAME (nitric oxide synthase inhibitor, 100 nmol) and L-arginine (Precursor of nitric oxide, 200 nmol) were injected instead of B5063. Then the amount of cumulative food was measured at 30, 60 and 120 min after injection. Obtained data showed, injection visfatin (2 and 4 µg) increased food intake compared to control group (P < 0.05). Co-injection of the B5063 + Visfatin decreased visfatin-induced hyperphagia compared to control group (P < 0.05). Co-injection of the L-NAME + Visfatin amplified visfatin-induced hyperphagia compared to control group (P < 0.05). The result showed that visfatin has hyperphagic role and this effect mediates via NPY1 and nitric oxide system in neonatal chicken.

Mindfulness meditation modulates stress-eating and its neural correlates.

Stress-related overeating can lead to excessive weight gain, increasing the risk of metabolic and cardiovascular disease. Mindfulness meditation has been demonstrated to reduce stress and increase interoceptive awareness and could, therefore, be an effective intervention for stress-related overeating behavior. To investigate the effects of mindfulness meditation on stress-eating behavior, meditation-naïve individuals with a tendency to stress-eat (N = 66) participated in either a 31-day, web-based mindfulness meditation training or a health training condition. Behavioral and resting-state fMRI data were acquired before and after the intervention. Mindfulness meditation training, in comparison to health training, was found to significantly increase mindfulness while simultaneously reducing stress- and emotional-eating tendencies as well as food cravings. These behavioral results were accompanied by functional connectivity changes between the hypothalamus, reward regions, and several areas of the default mode network in addition to changes observed between the insula and somatosensory areas. Additional changes between seed regions (i.e., hypothalamus and insula) and brain areas attributed to emotion regulation, awareness, attention, and sensory integration were observed. Notably, these changes in functional connectivity correlated with behavioral changes, thereby providing insight into the underlying neural mechanisms of the effects of mindfulness on stress-eating.Clinical trial on the ISRCTN registry: trial ID ISRCTN12901054.

Early childhood appetitive traits and eating disorder symptoms in adolescence: a 10-year longitudinal follow-up study in the Netherlands and the UK.

BACKGROUND: Obesity and eating disorders commonly co-occur and might share common risk factors. Appetite avidity is an established neurobehavioural risk factor for obesity from early life, but the role of appetite in eating disorder susceptibility is unclear. We aimed to examine longitudinal associations between appetitive traits in early childhood and eating disorder symptoms in adolescence. METHODS: In this longitudinal cohort study, we used data from Generation R (based in Rotterdam, the Netherlands) and Gemini (based in England and Wales). Appetitive traits at age 4-5 years were measured using the parent-reported Child Eating Behaviour Questionnaire. At age 12-14 years, adolescents self-reported on overeating eating disorder symptoms (binge eating symptoms, uncontrolled eating, and emotional eating) and restrictive eating disorder symptoms (compensatory behaviours and restrained eating). Missing data on covariates were imputed using Multivariate Imputation via Chained Equations. Ordinal and binary logistic regressions were performed in each cohort separately and adjusted for confounders. Pooled results were obtained by meta-analyses. Sensitivity analyses were performed on complete cases using inverse probability weighting. FINDINGS: The final study sample included 2801 participants from Generation R and 869 participants from Gemini. Pooled findings after meta-analyses showed that higher food responsiveness in early childhood increased the odds of binge eating symptoms (odds ratio [OR]pooled 1·47, 95% CI 1·26-1·72), uncontrolled eating (1·33, 1·21-1·46), emotional eating (1·26, 1·13-1·41), restrained eating (1·16, 1·06-1·27), and compensatory behaviours (1·18, 1·08-1·30) in adolescence. Greater emotional overeating in early childhood increased the odds of compensatory behaviours (1·18, 1·06-1·33). By contrast, greater satiety responsiveness in early childhood decreased the odds of compensatory behaviours in adolescence (0·89, 0·81-0·99) and uncontrolled eating (0·86, 0·78-0·95) in adolescence. Slower eating in early childhood decreased the odds of compensatory behaviours (0·91, 0·84-0·99) and restrained eating (0·90, 0·83-0·98) in adolescence. No other associations were observed. INTERPRETATION: In this study, higher food responsiveness in early childhood was associated with a higher likelihood of self-reported eating disorder symptoms in adolescence, whereas greater satiety sensitivity and slower eating were associated with a lower likelihood of some eating disorder symptoms. Appetitive traits in children might be early neurobehavioural risk factors for, or markers of, subsequent eating disorder symptoms. FUNDING: MQ Mental Health Research, Rosetrees Trust, ZonMw.

Associations between sleep and appetitive traits in higher-income preschoolers: A six-month study.

BACKGROUND: Short sleep is consistently linked with childhood obesity, possibly via disrupting appetite hormones and increasing food responsiveness. Few studies have objectively examined this association in early childhood. OBJECTIVE: To evaluate associations of sleep quantity and quality with child appetitive traits and eating in the absence of hunger (EAH) in a higher-income cohort of 86 preschool-age children (age 4.0 ± 0.8 years; 42% female; 93% non-Hispanic white, Northern New England, US). METHODS: Children's sleep duration and quality were assessed via parent report (Children's Sleep Habits Questionnaire, CSHQ) at baseline and 6-month follow-up and via accelerometry at baseline. Parents also completed the Child Eating Behaviors Questionnaire to assess the child's appetitive traits. EAH, an objective measure of overeating, was observed at baseline during an in-person visit. Associations between sleep measures and appetitive traits were examined with linear mixed-effect or linear regression models, as appropriate, adjusting for child age, sex, and household income. RESULTS: Shorter sleep duration per parent report was associated with less satiety responsiveness (standardized ß = 0.14, 95% CI: 0.01, 0.26; p = 0.03). Further, satiety responsiveness was inversely related to EAH (Pearson's r = -0.35, p = 0.02). No associations were found between accelerometer-measured sleep parameters and appetitive traits, and no sleep measures were related to EAH. CONCLUSIONS: Shorter usual sleep, per the parent report, was cross-sectionally associated with reduced satiety responsiveness in this sample of higher-income preschoolers. Future studies should consider whether socioeconomic status may modify the impact of poor sleep on appetitive traits in early childhood.

The Prader-Willi syndrome Profile: validation of a new measure of behavioral and emotional problems in Prader-Willi syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is a rare, neurodevelopmental disorder caused by the lack of expression of paternally imprinted genes on chromosome 15q11-13. PWS features a complex behavioral phenotype, including hyperphagia, anxiety, compulsivity, rigidity, repetitive speech, temper outbursts, aggressivity, and skin-picking. Questionnaires exist for measuring hyperphagia, but not for the aggregation of other problems that are distinctive to PWS. A PWS-specific tool is needed for phenotypic research, and to help evaluate treatment efficacy in future clinical trials aimed at attenuating PWS's hyperphagia and related problems. In this 4-phase study, we leveraged our expertise in PWS with feedback from families and specialists to validate the PWS Profile, a novel, informant-based measure of behavioral and emotional problems in this syndrome. RESULTS: The authors developed a bank of 73 items that tapped both common and less frequent but clinically significant problems in PWS (Phase 1). An iterative feedback process with families and stakeholders was used to ensure content and construct validity (Phase 2). After adding, omitting, or revising items, in Phase 3, we pilot tested the measure in 112 participants. Results were reviewed by an international team of PWS specialists and revised again (Phase 3). The final, 57-item Profile was then administered to 761 participants (Phase 4). Principal component factor analyses (n = 873) revealed eight conceptually meaningful factors, accounting for 60.52% of test variance, and were readily interpretated as: Rigidity, Insistence; Aggressive Behaviors; Repetitive Questioning, Speech; Compulsive Behaviors; Depression, Anxiety; Hoarding; Negative Distorted Thinking; and Magical Distorted Thinking. Factors were internally consistent and showed good test-retest reliability and convergent validity with existent measures of behavioral problems. Profile factors were not related to IQ, BMI, or parental SES. Three Profile factors differed across PWS genetic subtypes. Age and gender differences were found in only one Profile factor, Hoarding. CONCLUSIONS: The PWS Profile is a valid, psychometrically-sound questionnaire that already has shown responsivity to treatment in a previous clinical trial. The Profile can extend the reach of future clinical trials by evaluating the impact of novel agents not only on hyperphagia, but also on the emotional and behavioral problems that characterize PWS.

Hyperphagia and impulsivity: use of self-administered Dykens' and in-house impulsivity questionnaires to characterize eating behaviors in children with severe and early-onset obesity.

BACKGROUND: The determinants of early-onset obesity (< 6 years) are not completely elucidated, however eating behavior has a central role. To date no study has explored eating behavior in children with severe, early-onset obesity. Self-administered questionnaire data from these children were examined to evaluate eating behavior and the etiology of early-onset obesity. METHODS: Children with severe, early-onset obesity (body mass index [BMI] > International Obesity Task Force [IOTF] 30) of different etiologies (hypothalamic obesity [HO], intellectual disability with obesity [IDO], common polygenic obesity [CO]) were prospectively included. BMI history and responses from the Dykens' Hyperphagia Questionnaire and an in-house Impulsivity Questionnaire at first visit were compared between groups. RESULTS: This cohort of 75 children (39 girls; mean age ± standard deviation [SD] 10.8 ± 4.4 years) had severe, early-onset obesity at an age of 3.8 ± 2.7 years, with a BMI Z-score of 4.9 ± 1.5. BMI history varied between the 3 groups, with earlier severe obesity in the HO group versus 2 other groups (BMI > IOTF40 at 3.4 ± 1.6 vs. 4.6 ± 1.6 and 8.4 ± 4.1 years for the IDO and CO groups, respectively [P < 0.01]). Absence of adiposity rebound was more prevalent in the HO group (87% vs. 63% and 33% for the IDO and CO groups, respectively [P < 0.01]). The Dykens' mean total score for the cohort was 22.1 ± 7.2 with no significant between-group differences. Hyperphagia (Dykens' score > 19) and impulsivity (score > 7) were found in 50 (67%) and 11 children (15%), respectively, with no difference between the HO, IDO and CO groups regarding the number of patients with hyperphagia (10 [67%], 14 [74%], and 26 [63%] children, respectively) or impulsivity (2 [13%], 1 [7%], and 8 [19%] children, respectively). Children with food impulsivity had significantly higher total and severity scores on the Dykens' Questionnaire versus those without impulsivity. CONCLUSION: The Dykens' and Impulsivity questionnaires can help diagnose severe hyperphagia with/without food impulsivity in children with early-onset obesity, regardless of disease origin. Their systematic use can allow more targeted management of food access control in clinical practice and monitor the evolution of eating behavior in the case of innovative therapeutic targeting hyperphagia.

Bardet-Biedl syndrome: A focus on genetics, mechanisms and metabolic dysfunction.

Bardet-Biedl syndrome (BBS) is a rare, monogenic, multisystem disorder characterized by retinal dystrophy, renal abnormalities, polydactyly, learning disabilities, as well as metabolic dysfunction, including obesity and an increased risk of type 2 diabetes. It is a primary ciliopathy, and causative mutations in more than 25 different genes have been described. Multiple cellular mechanisms contribute to the development of the metabolic phenotype associated with BBS, including hyperphagia as a consequence of altered hypothalamic appetite signalling as well as alterations in adipocyte biology promoting adipocyte proliferation and adipogenesis. Within this review, we describe in detail the metabolic phenotype associated with BBS and discuss the mechanisms that drive its evolution. In addition, we review current approaches to the metabolic management of patients with BBS, including the use of weight loss medications and bariatric surgery. Finally, we evaluate the potential of targeting hypothalamic appetite signalling to limit hyperphagia and induce clinically significant weight loss.

Two Adverse Early Life Events Induce Differential Changes in Brain CRH and Serotonin Systems in Rats along with Hyperphagia and Depression.

BACKGROUND: Different types of stress inflicted in early stages of life elevate the risk, among adult animals and humans, to develop disturbed emotional-associated behaviors, such as hyperphagia or depression. Early-life stressed (ELS) adults present hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis, which is a risk factor associated with mood disorders. However, the prevalence of hyperphagia (17%) and depression (50%) is variable among adults that experienced ELS, suggesting that the nature, intensity, and chronicity of the stress determines the specific behavioral alteration that those individuals develop. METHODS: We analyzed corticosterone serum levels, Crh, GR, Crhr1 genes expression in the hypothalamic paraventricular nucleus, amygdala, and hippocampus due to their regulatory role on HPA axis in adult rats that experienced maternal separation (MS) or limited nesting material (LNM) stress; as well as the serotonergic system activity in the same regions given its association with the corticotropin-releasing hormone (CRH) pathway functioning and with the hyperphagia and depression development. RESULTS: Alterations in dams' maternal care provoked an unresponsive or hyper-responsive HPA axis function to an acute stress in MS and LNM adults, respectively. The differential changes in amygdala and hippocampal CRH system seemed compensating alterations to the hypothalamic desensitized glucocorticoids receptor (GR) in MS or hypersensitive in LNM. However, both adult animals developed hyperphagia and depression-like behavior when subjected to the forced-swimming test, which helps to understand that both hypo and hypercortisolemic patients present those disorders. CONCLUSION: Different ELS types induce neuroendocrine, brain CRH and 5-hydroxytriptamine (5-HT) systems' alterations that may interact converging to develop similar maladaptive behaviors.

Separate gut-brain circuits for fat and sugar reinforcement combine to promote overeating.

Food is a powerful natural reinforcer that guides feeding decisions. The vagus nerve conveys internal sensory information from the gut to the brain about nutritional value; however, the cellular and molecular basis of macronutrient-specific reward circuits is poorly understood. Here, we monitor in vivo calcium dynamics to provide direct evidence of independent vagal sensing pathways for the detection of dietary fats and sugars. Using activity-dependent genetic capture of vagal neurons activated in response to gut infusions of nutrients, we demonstrate the existence of separate gut-brain circuits for fat and sugar sensing that are necessary and sufficient for nutrient-specific reinforcement. Even when controlling for calories, combined activation of fat and sugar circuits increases nigrostriatal dopamine release and overeating compared with fat or sugar alone. This work provides new insights into the complex sensory circuitry that mediates motivated behavior and suggests that a subconscious internal drive to consume obesogenic diets (e.g., those high in both fat and sugar) may impede conscious dieting efforts.

Astrocytic Dagla Deletion Decreases Hedonic Feeding in Female Mice.

Introduction: Endocannabinoids and exogenous cannabinoids are potent regulators of feeding behavior and energy metabolism. Stimulating cannabinoid receptor signaling enhances appetite, particularly for energy-dense palatable foods, and promotes energy storage. To elucidate the underlying cellular mechanisms, we investigate here the potential role of astrocytic endocannabinoid 2-arachidonoylglycerol (2-AG). Astrocytes provide metabolic support for neurons and contribute to feeding regulation but the effect of astrocytic 2-AG on feeding is unknown. Materials and Methods: We generated mice lacking the 2-AG synthesizing enzyme diacylglycerol lipase alpha (Dagla) in astrocytes (GLAST-Dagla KO) and investigated hedonic feeding behavior in male and female mice. Body weight and baseline water and food intake was characterized; additionally, the mice went through milk, saccharine, and sucrose preference tests in fed and fasted states. In female mice, the estrous cycle stages were identified and plasma levels of female sex hormones were measured. Results: We found that the effects of the inducible astrocytic Dagla deletion were sex-specific. Acute milk preference was decreased in female, but not in male mice and the effect was most evident in the estrus stage of the cycle. This prompted us to investigate sex hormone profiles, which were found to be altered in GLAST-Dagla KO females. Specifically, follicle-stimulating hormone was elevated in the estrus stage, luteinizing hormone in the proestrus, and progesterone was increased in both proestrus and estrus stages of the cycle compared with controls. Conclusions: Astrocytic Dagla regulates acute hedonic appetite for palatable food in females and not in males, possibly owing to a deregulated female sex hormone profile. It is plausible that endocannabinoid production by astrocytes at least partly contributes to the greater susceptibility to overeating in females. This finding may also be important for understanding the effects of exogenous cannabinoids on sex hormone profiles.