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Background: Prader–Willi syndrome (PWS), a genetically determined disorder, the most frequent cause of early onset obesity, is associated with physical and cognitive dysfunctions and behavioural disturbances; these disturbances are frequently treated with psychotropic medication. The aim of this cross‐sectional study was to describe the characteristics of the first large national sample of persons with PWS in Spain and analyse the relationships of those characteristics with key demographic and clinical factors, particularly with obesity and the regular use of psychotropic medication. Methods: Participants were recruited among all members of the Spanish Prader–Willi Association who agreed to take part in the study and fulfilled its inclusion criteria. Family and patient demographic features, family size and birth order, intelligence quotient (IQ), anthropometric measures, lifestyle habits, behavioural disturbances (with the Aberrant Behavior Checklist) and clinical data, as well as use of psychotropic drugs and their side effects (with the UKU scale), were collected in genetically confirmed cases of PWS. Bivariate and logistic regression analyses were used for determining the associations of demographic and clinical factors with both obesity and the regular use of psychotropic medication. Results: The cohort included 177 participants (aged 6–48 years), that is, 90 (50.8%) males and 87 (49.2%) females. Behavioural disturbances were present in a range of 75% to 93% of participants; psychotropic medication was prescribed to 81 (45.8%) of them. Number of siblings showed a direct correlation with IQ, especially among males, and inappropriate speech was more intense in only‐child females. Obesity was, in parallel, strongly associated with ascending age and with not being currently under growth hormone (GH) treatment. Participants taking any psychotropic medication were characterised by more frequent age ≥30 years, high level of hyperactivity and a psychiatric diagnosis. Conclusions: Characterisation of persons with PWS in Spain confirms their physical and behavioural phenotype and supports the long‐term application of GH therapy and the rational use of psychotropic medication. [ABSTRACT FROM AUTHOR]

Eating-related problems (e.g., binge eating (BE)) and impaired quality of life (QoL) is more prevalent in children with overweight and obesity. This study aimed to investigate changes in self-reported overeating (OE), BE, and QoL in children with overweight or obesity attending multicomponent 10-week lifestyle camps with a 52-weeks follow-up. Additionally, the study sought to investigate whether self-reported OE/BE before camp was associated with changes in QoL. Children aged 7 to 14-years could attend camp if they had overweight/obesity, were lonely, unhappy, or had social or family-related problems. In this study only children with overweight and obesity were included (n:185). OE, BE, and QoL were measured using self-reported questionnaires. In total, 38 % of the children reported regular BE at baseline. Regular OE, occasional BE, and occasional OE was reported by 14 %, 13 %, and 11 %, respectively, while 24 % reported no eating-related problems. The relative risk of experiencing eating-related problems decreased at 10-weeks compared to baseline. Additionally, the probability of regular OE (RR 0.12 (95 % CI 0.04;0.38) (X2 = 8.44, p = 0.004)) and regular BE (RR 0.01 (95 % CI 0.00;0.11) (X2 = 9.91, p = 0.002)) remained lower at 52-weeks relative to baseline. All QoL dimensions improved after camp, and the presence of self-reported OE and regular BE at baseline was significantly associated with lower QoL at baseline, 10 and 52-weeks. Children self-reporting OE and BE may be a particular vulnerable group that needs more support from camp staff and healthcare professionals to improve QoL. clinicaltrials.gov with ID: NCT04522921 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) is a growth factor that promotes the survival and growth of developing neurons. It also enhances circuit formation to synaptic transmission for mature neurons in the brain. However, reduced BDNF expression and single nucleotide polymorphisms (SNP) are reported to be associated with functional deficit and disease development in the brain, suggesting that BDNF is a crucial molecule for brain health. Interestingly, BDNF is also expressed in the hypothalamus in appetite and energy metabolism. Previous reports demonstrated that BDNF knockout mice exhibited overeating and obesity phenotypes remarkably. Therefore, we could raise a hypothesis that the loss of function of BDNF may be associated with metabolic syndrome and peripheral diseases. In this review, we describe our recent finding that BDNF knockout mice develop metabolic dysfunction-associated steatohepatitis and recent reports demonstrating the role of one of the BDNF receptors, TrkB-T1, in some peripheral organ functions and diseases, and would provide an insight into the role of BDNF beyond the brain. [ABSTRACT FROM AUTHOR]

BACKGROUND: Eating patterns such as breakfast consumption and fruit and vegetable intake have been associated with academic achievement and cognitive function. METHOD: The purpose of this study was to learn more about psychological (emotion‐driven eating) and behavioral (over‐eating) eating patterns and motives, and the roles of body image, academic achievement (reading and math), and social supports (peer acceptance and school attachment), among 378 fourth‐grade students (55% boys) from 14 classrooms across 6 schools within a large Midwestern urban area. RESULTS: Results were analyzed through a 2‐group (male and female) path analysis. Boys' overeating (R2 = 9%) was not significantly predicted. Their emotional eating (R2 = 22.2%) was negatively, significantly predicted by peer acceptance and interaction of peer acceptance and school attachment. Girls' overeating (R2 = 13.6%) was negatively, significantly predicted by positive body image. Girls' emotional eating (R2 = 24.1%) was negatively significantly predicted by positive body image, math scores, and peer acceptance. CONCLUSIONS: Boys' and girls' eating patterns are differentially affected by their school experiences. [ABSTRACT FROM AUTHOR]

Assessing the seasonal changes in body condition (BC) of animals is important for understanding their reproduction and survival, as well as human–animal interaction. Visual or photographic assessment of BC has, however, been limited to species in open habitats or to specific times and locations. To noninvasively assess the seasonal changes in the entire local population of brown bears (Ursus arctos) inhabiting the forest habitat in eastern Hokkaido, Japan, we evaluated their BC using camera-trapping during 2015–2017. We assigned a 5-point BC score (BCS) for each individual based on the images, and examined seasonal changes in BCS by sex–age classes. Out of the 1,714 events in which brown bears were recorded, sex–age classes including adult males, subadults, females with offspring, and solitary adult females, could be determined in 887 events. Overall, BCS tended to decrease from spring to summer, with the lowest value in July, and tended to increase toward autumn, with the highest value in November. The BCS of adult male bears showed the highest seasonal variation, whereas that of subadults showed the least variation. Adult females, both solitary and those with offspring, showed intermediate seasonal variation in BCS compared with adult males and subadults. These seasonal changes were considered to be a general pattern and point to the amount of accumulated body fat. Adult males have a larger home range and, because of their social dominance, can exploit higher quality resources than can be exploited by other sex–age classes, which results in them being able to accumulate relatively more fat during hyperphagia. Females with offspring tended to have a lesser increase in BCS after August and lower BCS in autumn than did solitary adults. We were able to demonstrate the possibility of evaluating the BC of individuals and their seasonal changes by examining BCS based on the videos taken by camera traps. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract This study examined the effects of exercise and detraining at a young age on fat accumulation in various organs. Four‐week‐old male Otsuka Long‐Evans Tokushima Fatty (OLETF) rats were assigned to either the non‐exercise sedentary (OLETF Sed) or exercise groups. The exercise group was subdivided into two groups: exercise between 4 and 12 weeks of age (OLETF Ex) and exercise between 4 and 6 weeks of age followed by non‐exercise between 6 and 12 weeks of age (OLETF DT). Body weight was significantly lower in the OLETF Ex group than in the OLETF Sed group at 12 weeks of age. Fat accumulation in the epididymal white adipose tissue, liver, and brown adipose tissue was suppressed in the OLETF Ex group. During the exercise period, body weight and food intake in the OLETF DT group were significantly lower than those in the OLETF Sed group. However, food intake was significantly higher in the OLETF DT group than in the OLETF Sed group after exercise cessation, resulting in extreme obesity with fatty liver and brown adipose tissue whitening. Detraining after early‐onset exercise promotes hyperphagia, causing extreme obesity. Overeating should be avoided during detraining periods in cases of exercise cessation at a young age.

Abstract Background The determinants of early-onset obesity ( 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 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.

Relevance. Prader–Willi syndrome (SPW) is a rare genetic disease associated with a predominant legion of the nervous system with subsequent involvement of other systems. The main signs of the syndrome part childhood hypotension, hypogonadism with hypogenitalism, morbid obesity, and impaired cognitive functions. Goal. Presentation of a rare case with consideration of the features of the clinical picture and course of SPW. Materials and methods. The medical history of patient A., 10 months old, who is undergoing examination and inpatient treatment in the 3rd ward. OBUZ ODKB, as well as the materials of the Pubmed platform. Results. The article presents a clinical case of Prader–Willi syndrome in a 10-month-old girl with the first signs in the prenatal period.

The modern obesogenic environment contains an abundance of food cues (e.g., sight, smell of food) as well cues that are associated with food through learning and memory processes. Food cue exposure can lead to food seeking and excessive consumption in otherwise food-sated individuals, and a high level of food cue responsivity is a risk factor for overweight and obesity. Similar food cue responses are observed in experimental rodent models, and these models are therefore useful for mechanistically identifying the neural circuits mediating food cue responsivity. This review draws from both experimental rodent models and human data to characterize the behavioral and biological processes through which food-associated stimuli contribute to overeating and weight gain. Two rodent models are emphasized - cue-potentiated feeding and Pavlovian-instrumental transfer - that provide insight in the neural circuits and peptide systems underlying food cue responsivity. Data from humans are highlighted that reveal physiological, psychological, and neural mechanisms that connect food cue responsivity with overeating and weight gain. The collective literature identifies connections between heightened food cue responsivity and obesity in both rodents and humans, and identifies underlying brain regions (nucleus accumbens, amygdala, orbitofrontal cortex, hippocampus) and endocrine systems (ghrelin) that regulate food cue responsivity in both species. These species similarities are encouraging for the possibility of mechanistic rodent model research and further human research leading to novel treatments for excessive food cue responsivity in humans.

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. [ABSTRACT FROM AUTHOR]

Objective: This pilot study aims to investigate the feasibility, acceptability, and potential effectiveness of online Compassion Focused Therapy for overeating (CFT‐OE). Method: Eighteen Portuguese women seeking treatment for overeating were enrolled in this study, and 15 participants completed the CFT‐OE. This was a single‐arm study. Participants were assessed at pre‐ and post‐intervention and 3‐month follow‐up. All participants completed measures assessing binge eating, cognitive restraint, uncontrolled eating, emotional eating, general eating psychopathology, general and body shame, self‐criticism, self‐compassion, and fears of self‐compassion. Results: The treatment attrition rate was 16.7%, which is relatively low compared to other similar online interventions. Participants gave positive feedback on the program and indicated they would recommend it to people with similar difficulties. CFT‐OE improved self‐compassion and reduced eating psychopathology symptoms, general and body shame, self‐criticism, and fears of self‐compassion. Clinical significance analysis showed that the majority of participants were classified as in recovery in all measures at post‐intervention and 3‐month follow‐up. Discussion: Preliminary results suggest that the online CFT‐OE program is an acceptable and feasible intervention. Results also suggest that CFT‐OE is beneficial for the treatment of women with difficulties with overeating. A future randomized controlled trial is necessary to establish the effectiveness of the CFT‐OE. Public significance: This study indicates that online CFT‐OE is a feasible and adequate intervention for women who struggle with overeating. This therapy showed promising results in reducing eating disorder symptoms, shame, and self‐criticism and improving self‐compassion. As an online intervention, CFT‐OE may be more accessible and offer an alternative to in‐person therapy. [ABSTRACT FROM AUTHOR]

Maternal obesity and/or high-fat diet (HF) consumption can disrupt appetite regulation in their offspring, contributing to transgenerational obesity and metabolic diseases. As fatty acids (FAs) play a role in appetite regulation, we investigated the maternal and fetal levels of FAs as potential contributors to programmed hyperphagia observed in the offspring of obese dams. Female mice were fed either a control diet (CT) or HF prior to mating, and fetal and maternal blood and tissues were collected at 19 days of gestation. Elevated levels of linoleic acid were observed in the serum of HF dams as well as in the serum of their fetuses. An increased concentration of eicosadienoic acid was also detected in the hypothalamus of female HF-O fetuses. HF-O male fetuses showed increased hypothalamic neuropeptide Y (Npy) gene expression, while HF-O female fetuses showed decreased hypothalamic pro-opiomelanocortin (POMC) protein content. Both male and female fetuses exhibited reduced hypothalamic neurogenin 3 (NGN-3) gene expression. In vitro experiments confirmed that LA contributed to the decreased gene expression of Pomc and Ngn-3 in neuronal cells. During lactation, HF female offspring consumed more milk and had a higher body weight compared to CT. In summary, this study demonstrated that exposure to HF prior to and during gestation alters the FA composition in maternal serum and fetal serum and hypothalamus, particularly increasing n-6, which may play a role in the switch from POMC to NPY neurons, leading to increased weight gain in the offspring during lactation. [ABSTRACT FROM AUTHOR]

Introduction: Craniopharyngiomas are rare brain tumours (incidence 1.1–1.7 cases/million/year). Although non-malignant, craniopharyngioma causes major endocrine and visual morbidities including hypothalamic obesity, yet mechanisms leading to obesity are poorly understood. This study investigated the feasibility and acceptability of eating behaviour measures in patients with craniopharyngioma to inform the design of future trials. Methods: Patients with childhood-onset craniopharyngioma and controls matched for sex, pubertal stage, and age were recruited. After an overnight fast, participants received the following measures: body composition, resting metabolic rate, oral glucose tolerance test including magnetic resonance imaging (patients only), appetite ratings, eating behaviour, and quality of life questionnaires, ad libitum lunch, and an acceptability questionnaire. Data are reported as median ± IQR, with effect size measure (Cliff's delta) and Kendall's tau for correlations, due to the small sample size. Results: Eleven patients (median age = 14 years; 5 F/6 M) and matched controls (median age = 12 years; 5 F/6 M) were recruited. All patients had received surgery, and 9/11 also received radiotherapy. Hypothalamic damage post-surgery was graded (Paris grading): grade 2 n = 6; grade 1 n = 1; grade 0 n = 2. The included measures were deemed highly tolerable by participants and their parent/carers. Preliminary data suggest a difference in hyperphagia between patients and controls (d = 0.5), and a relationship between hyperphagia with body mass index standard deviation score (BMISDS) in patients (τ = 0.46). Discussion: These findings demonstrate that eating behaviour research is feasible and acceptable to craniopharyngioma patients and there is an association between BMISDS and hyperphagia in patients. Thus, food approach and avoidance behaviours may be useful targets for interventions to manage obesity in this patient group. [ABSTRACT FROM AUTHOR]

Context Craniopharyngioma (CP) is a rare brain tumor associated with severe comorbidities that reduce survivor health-related quality of life (HRQOL). However, CP impact on caregivers is unknown. Objective To measure caregiver burden and examine its relationship to survivor HRQOL and other determinants in CP. Methods Eighty-two participants who self-identified as caregivers of CP survivors responded to an online survey including caregiver-reported Pediatric Quality of Life Inventory (PedsQL), and the Zarit Burden Interview (ZBI). Results Caregivers reported an average of 13 out of 29 health conditions in survivors following tumor treatment, including excess weight, hypopituitarism, fatigue, mood, cognition, social issues, temperature dysregulation, visual impairment, and sleep problems. Strikingly, 70% of survivors who experienced obesity also experienced hyperphagia. ZBI scores were moderate with a median of 37. PedsQL total scores were poor with a median of 46.2. ZBI scores were independent of caregiver level of education and care duration. Both scores were independent of income, survivor age, gender, age at diagnosis, or tumor recurrence. In contrast, both scores depended on the number (P <.001) and the type of survivor health problems, with significantly worse scores for caregivers or survivors with symptoms of hypothalamic dysfunction (P <.001) including hyperphagia but not obesity. PedsQL total scores significantly predicted ZBI scores (P <.001). Conclusion Survivor poly-symptomatology predicted and incurred significant caregiver burden. Our study separated hyperphagia and obesity and identified hyperphagia and other hypothalamic dysfunction symptoms as understudied issues. Altogether, these findings draw particular attention to the unmet needs of CP survivors and their caregivers. [ABSTRACT FROM AUTHOR]

Context: Prader-Willi syndrome (PWS) is a complex disorder combining hypothalamic dysfunction, neurodevelopmental delay, hypotonia, and hyperphagia with risk of obesity and its complications. PWS is caused by the loss of expression of the PWS critical region, a cluster of paternally expressed genes on chromosome 15q11.2-q13. As life expectancy of patients with PWS increases, age-related diseases like malignancies might pose a new threat to health. Objective: To investigate the prevalence and risk factors of malignancies in patients with PWS and to provide clinical recommendations for cancer screening. Methods: We included 706 patients with PWS (160 children, 546 adults). We retrospectively collected data from medical records on past or current malignancies, the type of malignancy, and risk factors for malignancy. Additionally, we searched the literature for information about the relationship between genes on chromosome 15q11.2-q13 and malignancies. Results: Seven adults (age range, 18-55 years) had been diagnosed with a malignancy (acute lymphoblastic leukemia, intracranial hemangiopericytoma, melanoma, stomach adenocarcinoma, biliary cancer, parotid adenocarcinoma, and colon cancer). All patients with a malignancy had a paternal 15q11-13 deletion. The literature review showed that several genes on chromosome 15q11.2-q13 are related to malignancies. Conclusion: Malignancies are rare in patients with PWS. Therefore, screening for malignancies is only indicated when clinically relevant symptoms are present, such as unexplained weight loss, loss of appetite, symptoms suggestive of paraneoplastic syndrome, or localizing symptoms. Given the increased cancer risk associated with obesity, which is common in PWS, participation in national screening programs should be encouraged. [ABSTRACT FROM AUTHOR]

Prader-Willi syndrome (PWS) is a complex genetic disorder caused by lack of expression of genes on the paternally inherited chromosome 15q11.2-q13 region, known as the Prader Willi critical region. Nutritional clinical manifestations change with age and are described in four different phases. The phases span both extremes of the nutritional spectrum, beginning with an infant with poor sucking reflexes and failure to thrive then progressing to an adolescent who may have hyperphagia and be at risk for obesity. The phenotype is likely due to hypothalamic dysfunction due to genetic changes in the Prader Willi critical region. Researchers are examining the pathological mechanisms that determine the disease course.

Disinhibited eating behaviors (e.g., loss of control eating (LOC) and eating in the absence of hunger (EAH)) contribute to overeating and obesity. This study aimed to evaluate whether these traits are related in parent-child dyads and how the reporter of child eating behavior (parent or child) impacts this relationship. Two-hundred and ninety treatment-seeking children, ages 8-13, with overweight or obesity (BMI percentile for age and sex 85-99.9%) and their parents were included. LOC and EAH were assessed by child report for self, parent report for self, and parent report for child. Parent and child disinhibited eating behaviors were related only when parents reported on both their own and their child's eating behaviors (p-values < 0.04). Child report of LOC and EAH for self was not associated with parent report of LOC and EAH for self (p-values > 0.05). There was a significant interaction between parent's EAH and BMI as it related to parent report of child EAH (B = 0.02; SE = 0.005; p = 0.004) such that parents with lower BMI reported their own EAH to be lower than parents with higher BMI, but parent report of child EAH was similar regardless of the parent's BMI. Disinhibited eating behaviors were related only when a single parent reported on both their own and their child's behavior, suggesting a potential reporting bias. Given that the relation between parent and child disinhibited eating behaviors varies based on who is reporting the child's behavior, it may be important to consider both parent and child report when designing research studies or in clinical settings while also recognizing potential reporting biases.

Abstract Objective Prader‐Willi syndrome (PWS) is the most frequently diagnosed genetic cause of early childhood obesity. Individuals with PWS typically progress through 7 different nutritional phases during their lifetime. The main objective of this study was to assess potential factors, particularly insulin, that may be responsible for the weight gains in sub‐phase 2a and their role in the subsequent increase in fat mass and obesity in sub‐phase 2b and insatiable appetite in phase 3. Methods Fasting plasma insulin levels were measured in children with PWS between the ages of 0–12 years and in age‐matched non‐PWS participants with early‐onset major (clinically severe) obesity (EMO) and in healthy‐weight sibling controls (SC). Results Participants with PWS in nutritional phases 1a and 1b had plasma insulin levels comparable to SC. However, the transition from phase 1b up to phase 3 in the PWS group was accompanied by significant increases in insulin, coinciding in weight gains, obesity, and hyperphagia. Only individuals with PWS in phase 3 had comparable insulin levels to the EMO group who were higher than the SC group at any age. Conclusions Elevated insulin signaling is a probable trigger for weight gain and onset of hyperphagia in children with Prader‐Willi syndrome. Regulating insulin levels early in childhood before the onset of the early weight gain may be key in modulating the onset and severity of obesity and hyperphagia in individuals with PWS, as well as in other young children with non‐PWS early‐onset obesity. Preventing or reversing elevated insulin levels in PWS with pharmacological agents and/or through diet restrictions such as a combined low carbohydrate, low glycemic‐load diet may be a viable therapeutic strategy in combating obesity in children with PWS and others with early childhood obesity.

Abstract Objective Rare genetic diseases of obesity typically present with hyperphagia, a pathologic desire to consume food. Cost‐utility models assessing the value of treatments for these rare diseases will require health state utilities representing hyperphagia. This study estimated utilities associated with various hyperphagia severity levels. Methods Four health state vignettes were developed using published literature and clinician input to represent various severity levels of hyperphagia. Utilities were estimated for these health states in a time trade‐off elicitation study in a UK general population sample. Results In total, 215 participants completed interviews (39.5% male; mean age 39.1 years). Mean (SD) utilities were 0.98 (0.02) for no hyperphagia, 0.91 (0.10) for mild hyperphagia, 0.70 (0.30) for moderate hyperphagia, and 0.22 (0.59) for severe hyperphagia. Mean (SD) disutilities were −0.08 (0.10) for mild, −0.28 (0.30) for moderate, and −0.77 (0.58) for severe hyperphagia. Conclusions These data show increasing severity of hyperphagia is associated with decreased utility. Utilities associated with severe hyperphagia are similar to those of other health conditions severely impacting quality of life (QoL). These findings highlight that treatments addressing substantial QoL impacts of severe hyperphagia are needed. Utilities estimated here may be useful in cost‐utility models of treatments for rare genetic diseases of obesity.

Abstract Background Bardet-Biedl syndrome (BBS) is a rare, genetically heterogeneous obesity syndrome associated with hyperphagia. Given the early onset of BBS symptoms in childhood and multifaceted complications, this study aimed to quantify the caregiver burden associated with BBS. Methods A cross-sectional, multi-country survey of caregivers from the United States (US), United Kingdom (UK), Canada, and Germany was designed to quantify the extent of caregiver burden associated with obesity and hyperphagia symptoms (i.e., uncontrollable hunger) among patients with BBS. Results A total of 242 caregivers across the four countries met the inclusion criteria and completed the survey. The mean (standard deviation [SD]) age of the caregivers was 41.9 (6.7) years, and the mean (SD) age of individuals with BBS in their care was 12.0 (3.7) years. Hyperphagia contributed to a BBS diagnosis in 230 of 242 individuals (95.0%). On average, caregivers used eight different weight management approaches for those in their care and expressed a strong desire for more effective weight management methods. Based on the Impacts of Hyperphagia: Caregiver version, patients’ hyperphagia had a moderate-to-severe impact on caregiver mood (56.6%), sleep (46.6%), and relationships (48.0%). Caregivers reported experiencing a high level of personal strain (mean [SD], 17.1 [2.9]) and family impact (mean [SD] score, 26.0 [3.8]) due to BBS, as measured by the Revised Impact on Family Scale. Among caregivers in the workforce, there also was high impairment in total work productivity (mean [SD], 60.9% [21.4%]) due to caring for patients with BBS according to the Work Productivity and Activity Impairment. More than half (53%) of the caregivers reported spending over 5,000 out-of-pocket in local currency for medical expenses for the patient with BBS in their care. Conclusions Obesity and hyperphagia have negative impacts on the lives of caregivers of patients with BBS. The burden is demonstrated to be multifaceted, with various components that may interact with and confound each other, including intensive weight management efforts, productivity loses, impaired family dynamics and out-of-pocket medical expenses.

The Hyperphagia Questionnaire for Clinical Trials (HQ-CT) is an observer-reported outcome measure that has been widely used in interventional studies to assess changes in hyperphagic behaviors in individuals with Prader-Willi syndrome (PWS). However, HQ-CT scores in the wider PWS population and the general population have not been reported. Here we report HQ-CT scores from more than 400 individuals with PWS and 600 typical individuals, aged 5–26. Overall, HQ-CT scores were significantly higher in those with PWS compared to typically developing individuals at all ages evaluated. In addition, while HQ-CT scores in the typically developing population decreased with age, scores increased with age in PWS. To further understand the variability of HQ-CT scores in the PWS population, semi-structured interviews were conducted with caregivers of a small subset of adults with PWS who had unexpectedly low HQ-CT scores. These caregivers reported that strict adherence to a food routine, food security measures and supervised food preparation reduced the frequency and intensity of hyperphagic behaviors measured by HQ-CT. Thus, hyperphagic behaviors are captured by the HQ-CT for most individuals with PWS, but for some individuals residing in settings with highly structured food routines, HQ-CT scores may not fully reflect the extent of PWS-associated hyperphagia. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) and its complications can have debilitating, sometimes fatal consequences for afflicted individuals. The disease can be difficult to control, and therapeutic strategies to prevent T2D-induced tissue and organ damage are needed. Here we describe the results of administering a potent and selective inhibitor of Protein Kinase C (PKC) family members PKCα and PKCβ, Cmpd 1, in the ZSF1 obese rat model of hyperphagia-induced, obesity-driven T2D. Although our initial intent was to evaluate the effect of PKCα/β inhibition on renal damage in this model setting, Cmpd 1 unexpectedly caused a marked reduction in the hyperphagic response of ZSF1 obese animals. This halted renal function decline but did so indirectly and indistinguishably from a pair feeding comparator group. However, above and beyond this food intake effect, Cmpd 1 lowered overall animal body weights, reduced liver vacuolation, and reduced inguinal adipose tissue (iWAT) mass, inflammation, and adipocyte size. Taken together, Cmpd 1 had strong effects on multiple disease parameters in this obesity-driven rodent model of T2D. Further evaluation for potential translation of PKCα/β inhibition to T2D and obesity in humans is warranted. [ABSTRACT FROM AUTHOR]

Obesity represents a major health problem in the pediatric population with an increasing prevalence worldwide, associated with cardiovascular and metabolic disorders, and due to both genetic and environmental factors. Rare forms of obesity are mostly monogenic, and less frequently due to polygenic influence. Polygenic form of obesity is usually the common obesity with single gene variations exerting smaller impact on weight and is commonly non-syndromic. Non-syndromic monogenic obesity is associated with variants in single genes typically related to the hypothalamic leptin-melanocortin signalling pathway, which plays a key role in hunger and satiety regulation, thus body weight control. Patients with these genetic defects usually present with hyperphagia and early-onset severe obesity. Significant progress in genetic diagnostic testing has recently made for early identification of patients with genetic obesity, which guarantees prompt intervention in terms of therapeutic management of the disease. What is Known: • Obesity represents a major health problem among children and adolescents, with an increasing prevalence worldwide, associated with cardiovascular disease and metabolic abnormalities, and it can be due to both genetic and environmental factors. • Non-syndromic monogenic obesity is linked to modifications in single genes usually involved in the hypothalamic leptin-melanocortin signalling pathway, which plays a key role in hunger and satiety regulation. What is New: • The increasing understanding of rare forms of monogenic obesity has provided significant insights into the genetic causes of pediatric obesity, and our current knowledge of the various genes associated with childhood obesity is rapidly expanding. • A useful diagnostic algorithm for early identification of genetic obesity has been proposed, which can ensure a prompt intervention in terms of therapeutic management of the disease and an early prevention of the development of associated metabolic conditions. [ABSTRACT FROM AUTHOR]

This study utilized a U.S. national dataset of sexual and gender minority youth (SGMY) to examine the relationships between gender identity, sexual orientation, and overeating. Results indicate transgender/gender diverse (TGD) youth had a greater risk for overeating than their cisgender counterparts. Youth who identified their sexual orientation as queer, pansexual, or questioning were found to have greater odds of overeating compared to transgender/gender diverse (TGD) straight youth. Among ethno-racial identities, Asian SGMY had the lowest rates of overeating, while Native American and Middle Eastern/Arab SGMY presented the highest rates. Exercise and stress were explored as covariates, along with demographic factors. [ABSTRACT FROM AUTHOR]

Short Bowel Syndrome (SBS) is the major cause of chronic intestinal failure (IF) and requires parenteral nutrition (PN). After bowel resection, some patients develop spontaneous intestinal adaptations and hyperphagia. Since promoting oral energy intake contributes to PN weaning, this study aims to characterize hyperphagia in patients with SBS and identify its determinants. This observational retrospective study included adult patients with SBS who were followed at an expert PN center between 2006 and 2019, with at least 2 separate nutritional assessments. Exclusion criteria were: active neoplasia, alternative treatment for IF or appetite-affecting medication. Resting energy expenditure (REE) was calculated for each patient using the Harris–Benedict equation. Food Intake Ratio (FIR) was calculated by dividing the highest caloric oral intake by REE and hyperphagia was defined as FIR >1.5. Among the 59 patients with SBS included in this study, 82.6% had a FIR >1.5, including 15.5% with a FIR >3. Protein supplied approximately 16% of total energy intake while fat and carbohydrates provided 36% and 48%, respectively. The FIR was independent of gender and whether patients received oral nutrition alone (n = 28) or combined with PN (n = 31). The FIR was also not associated with residual small bowel length, nor the proportion of preserved colon. However, it was negatively correlated with the body mass index (BMI) of these patients (r = −0.533, p < 0.001), whether they had PN support or not. Patients with either a jejuno-colonic (n = 31) or a jejuno-ileal anastomosis (n = 9), had a significantly higher FIR compared to those with an end-jejunostomy (n = 18) (p < 0.05). However, no difference was found in the proportion of calories provided by protein, fat and carbohydrate between the 3 patients groups divided according to the SBS anatomical type. A large majority of patients with SBS exhibited a hyperphagia regardless of PN dependence or bowel length, which was inversely correlated with BMI. The presence of the colon in continuity, thus in contact with the nutritional flow, seems to favor a higher oral intake which is beneficial for the nutritional autonomy of patients. This raises the question of a role of colonic microbiota and hormones in this behavior. Finally, this study also revealed an unexpected discrepancy between recommended energy intakes from protein, fat and carbohydrate and the actual intake of patients with SBS. [ABSTRACT FROM AUTHOR]

Genetic disruption of key molecular components of the hypothalamic leptin–melanocortin pathway causes severe obesity in mice and humans. Physiological studies in people who carry these mutations have shown that the adipose tissue-derived hormone leptin primarily acts to defend against starvation. A lack of leptin causes an intense drive to eat and increases the rewarding properties of food, demonstrating that human appetite has a strong biological basis. Genetic studies in clinical- and population-based cohorts of people with obesity or thinness continue to provide new insights into the physiological mechanisms involved in weight regulation and identify molecular targets for weight loss therapy. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part II)'. [ABSTRACT FROM AUTHOR]

Simple Summary: Steroid-induced hepatopathy is the most important liver abnormality in dogs with hyperadrenocorticism (HAC). Serum activities of several liver enzymes increase in dogs with HAC. However, serum bile acids concentrations in dogs with HAC are poorly described. This study evaluated serum total bile acids concentrations and serum liver enzyme activities after trilostane treatment in dogs with HAC. Hyperadrenocorticism (HAC) often leads to vacuolar hepatopathy. The impact of trilostane treatment on serum total bile acids (SBAs) concentrations in dogs with HAC remains unknown. This study investigated SBAs concentrations in healthy dogs and those with HAC following trilostane therapy. Ten healthy dogs and fifteen dogs with HAC were prospectively enrolled. A biochemistry profile and pre- and post-prandial SBAs concentrations were determined in each dog. Dogs with HAC were reassessed at 1 and 3 months after the initiation of trilostane treatment. Dogs with HAC had significantly higher serum ALT, ALP, and GGT activities, and cholesterol, triglyceride, and pre-prandial SBAs concentrations compared to healthy dogs. After 3 months of trilostane treatment, polyuria/polydipsia and polyphagia were completely resolved in 42.8% and 35.7%, respectively. Significant improvements in serum ALT and ALP activities and cholesterol concentrations were observed within 1–3 months of trilostane treatment. However, pre- and post-prandial SBAs concentrations did not significantly decrease. These findings suggest that treatment with low-dose trilostane for 3 months appears to reduce serum liver enzyme activities, but not SBAs concentrations. Further investigation is warranted to explore the effects of low-dose trilostane treatment on SBAs concentrations for a longer duration or after achieving appropriate post-ACTH cortisol levels. [ABSTRACT FROM AUTHOR]

Rapid prenatal and postnatal weight gain seem to alter appetite regulation and hypothalamic functions through different pathways; however, little is known on how early life growth trajectories may influence appetitive traits in school-age. We aimed to explore the associations between weight trajectories from birth to 5 years and appetitive traits at 7. Participants were from the Generation XXI birth cohort (n 3855). Four weight trajectories were investigated: ' normal weight gain ' (closely overlaps the 50th percentile in the weight-for-age curve), ' weight gain during infancy ' (low birth weight and weight gain mainly during infancy), ' weight gain during childhood ' (continuous weight gain since birth) and ' persistent weight gain ' (always showing higher weight than the average). Appetitive traits were assessed through the Children's Eating Behaviour Questionnaire. Associations were tested using generalised linear models, adjusted for maternal and child characteristics. Compared with ' normal weight gain ', those in the other growth trajectories showed greater enjoyment of food and eating in response to food stimuli (i.e. Food Responsiveness) but were less able to compensate for prior food intake and ate faster at 7 (i.e. less Satiety Responsiveness and Slowness in Eating). Also, those with ' weight gain during infancy ' showed to have greater Emotional Overeating and less Emotional Undereating and were fussier. Associations were stronger if greater weight gain occurred during infancy. Early infancy seems to be a sensitive period in the development of later appetitive traits. The control of rapid growth during infancy, besides strategies focused on the overall environment where children are living, is necessary. [ABSTRACT FROM AUTHOR]

Background: Parental feeding practices (PFPs) are a key component of a child's food environment. Parent–child feeding relationships are hypothesised to be bidirectional; however, to date, few large prospective studies have examined this, instead focussing on unidirectional relationships. As such, the direction of relationships between PFPs and children's eating behaviours remains unclear. Methods: Data were from Gemini, a population‐based sample of children born in England and Wales in 2007. Children's eating behaviours and PFPs were measured at 15/16 months and 5 years using validated psychometric measures (n = 1,858 children). Bivariate Latent Change Score Modelling was used to examine the nature of relationships between PFPs and children's eating behaviours at 15/16 months and 5 years. Models were adjusted to account for clustering of twins within families and for sex of the child, socioeconomic status, gestational age and age of the child at measurement time points. Results: A reciprocal relationship was observed between instrumental feeding and emotional overeating, with greater instrumental feeding predicting greater increases in emotional overeating (β =.09; 0.03–0.15; p =.004) and vice versa (β =.09; 0.03–0.15; p =.005). Reciprocity was also observed between encouragement to eat nutritious foods and children's enjoyment of food, with greater encouragement predicting greater increases in enjoyment of food (β =.08; 0.02–0.13; p =.006) and vice versa (β =.07; 0.02–0.11; p =.003). Parent–child associations and child–parent associations were also observed. Conclusion: These findings are consistent with the hypothesis that certain feeding practices are used as a 'natural' response to a child expressing a greater interest in and enthusiasm for food, but at the same time, such practices impact the development of eating behaviours by nurturing and encouraging the expression of higher emotional overeating and greater enjoyment of food in preschool years. The findings provide important insights into the PFPs and eating behaviour traits that could be targeted as part of a tailored feeding intervention to support parents of children during the preschool formative years. [ABSTRACT FROM AUTHOR]

Prader-Willi Syndrome (PWS) is characterized by hyperphagia, an extreme and persistent hunger that emerges in early childhood. We used event-related potentials (ERPs) to objectively investigate brain responses to low- and high-calorie foods, animals, and household objects in 20 satiated adolescents with PWS. Late Positive Potential (LPP) responses to food images did not differ from non-food images. Rather, we observed larger ERPs to high-calorie foods relative to animal images (p=.001) in an earlier time window. These responses correlated with greater severity of hyperphagia (p =.01). Thus, hyperphagia associated with PWS may be due to altered satiety regulation rather than increased motivational salience. [ABSTRACT FROM AUTHOR]

Background: The genetic contribution to obesity is substantial and may underpin the altered pathophysiology. One such pathway involves melanocortin signaling in the hypothalamus. Genetic variants can cause dysregulation in the central melanocortin pathway that can result in early onset of hyperphagia and obesity. Clinically identifying patients who are at risk of known genetic mutations is challenging. The main purpose of this study was to identify associations between the clinico-demographical characteristics and the presence of a genetic mutation associated with obesity. Methods: We tested samples from 238 adult patients with class III obesity between October 2021 to February 2023 using next-generation sequencing (NGS) (Illumina, NovaSeq 6000 Sequencing System). The results were classified as "no variant identified" or "variant identified". Results: 107 patients (45%) had one or more gene mutation in the leptin–melanocortin pathway. All variants were heterozygous. The patients with a gene mutation had a BMI of 48.4 ± 0.8 kg/m2 (mean ± SEM), and those without a gene mutation had a BMI of 49.4 ± 0.7 kg/m2 (p = 0.4). The mean age of onset of obesity in patients with a gene mutation was 13.9 ± 1.3 years and for those without gene mutations was 11.5 ± 0.9 years (p = 0.1). The incidence of hyperphagia as a child was also not predictive (p = 0.4). Conclusions: Gene mutations associated with obesity in patients with a BMI > 40 kg/m2 are common. However, a patient's BMI, age of onset of obesity, or age of onset of hyperphagia did not help to differentiate which patients may be more likely to have genetic mutations associated with obesity. [ABSTRACT FROM AUTHOR]

Objective: Though prevalent, weight‐based discrimination is understudied and has been linked to disordered eating behaviors (DEB) among adolescents and adults. Sexual minority populations experience elevated risk of DEB, but little is known about the role of weight discrimination in this elevated risk. Methods: Participants were 1257 sexual minority women and men (ages 18–31 years) in the US Growing Up Today Study cohort. We examined cross‐sectional associations between weight discrimination victimization and three DEB in the past year: unhealthy weight control behaviors, overeating, and binge eating. Generalized estimating equations, adjusted for potential confounders, were used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs). Results: Three in 10 participants (31%) reported weight‐based discrimination victimization. Sexual minority young adults who reported weight‐based discrimination had greater relative prevalence of unhealthy weight control behaviors (PR [95% CI]: 1.92 [1.35, 2.74]), overeating (3.15 [2.24, 4.44]), and binge eating (3.92 [2.51, 6.13]), compared with those who reported no weight‐based discrimination. Associations with overeating and binge eating remained significant after adjusting for BMI. Discussion: The role of weight‐based discrimination, and its intersections with other forms of stressors for sexual minority young adults, must be included in efforts to advance eating disorder prevention for this underserved population. Public Significance: Three in 10 sexual minority young adults in this study had experienced weight‐based discrimination, a common but understudied form of discrimination. Sexual minority young adults who experienced weight‐based discrimination were at greater risk of disordered eating behaviors than those who had not experienced weight‐based discrimination. These findings suggest that weight‐based discrimination may be an important—and preventable—risk factor for disordered eating behaviors among sexual minority young adults. [ABSTRACT FROM AUTHOR]