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).

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.

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.

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.

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.

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.

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.

Genotype-phenotype correlation in Prader-Willi syndrome: A large-sample analysis in China.

The genotype-phenotype relationship in PWS patients is important for a better understanding of the clinical phenotype and clinical characteristics of different genotypes of PWS in children. We aimed to explore the influence of specific gene changes on the clinical symptoms of PWS and the value of early screening and early intervention of the condition. All data in this study were extracted from the database of the XiaoPang Weili Rare Disease Care Center. The collected information included basic demographics, maternal pregnancy information, endocrine abnormalities, growth and development abnormalities, and other clinical phenotypes. The relationships between genotypes and phenotypes in the major categories of PWS were analyzed. A total of 586 PWS cases with confirmed molecular diagnosis and genotyping were included in this study. Among them, 83.8% belonged to the deletion type, 10.9% the uniparental disomy (UPD) type, and 5.3% the imprinting defect (ID) type. Age-wide comparison among the three groups: The rate of hypopigmentation in the deletion group was higher than that in the UPD group (88.8% vs. 60.9%; p < 0.05); A total of 62 patients (14.2%) had epilepsy; and no statistical significance was found among the three groups (p = 0.110). Age-wide comparison between the deletion and non-deletion types: the rate of skin hypopigmentation and epilepsy in the deletion group was significantly higher than that in the non-deletion group (88.8% vs. 68.4%, p < 0.001; 15.9% vs. 7.6%, p = 0.040). The intergroup comparison for the >2-year age group: there were significant intergroup differences in the language development delay among the three groups (p < 0.001). The incidence of delayed language development was the highest in the deletion group, followed by the UPD group, and the lowest in the ID group. The rates of obesity and hyperphagia in the deletion group were also higher than those in the non-deletion group (71.1% vs. 58.9%, p = 0.041; 75.7% vs. 62.0%, p = 0.016). There are significant differences in the rates of skin hypopigmentation and language developmental delay among the deletion, UPD, and ID genotypes. The patients with deletion type had significantly higher rates of lighter skin color, obesity, hyperphagia, language developmental delay, and epilepsy. The results of this study will help clinicians better understand the impact of different PWS molecular etiologies on specific phenotypes.

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.

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.

The Relationship between Depressiveness and Eating Behaviors among Women.

(1) The objective of the study was to determine the relationship between depressiveness and the occurrence of eating disorders, i.e., emotional eating, uncontrolled eating, cognitive restraint of eating, and the risk of orthorexia. (2) The study was conducted among 556 women from the West Pomeranian Voivodeship (Poland). The study employed the diagnostic survey method using a questionnaire technique: The Beck Depression Inventory, the ORTO-15 Questionnaire, the Three-Factor Eating Questionnaire, and a sociodemographic questionnaire. (3) Higher depressiveness severity is associated with a higher score on the "Cognitive Restraint of Eating" scale. The authors' original study demonstrated a statistically significant relationship only between depressiveness and the "Uncontrolled Eating" subscale (p = 0.001). (4) The results of this study suggest that depressiveness is an important factor that contributes to a better understanding of eating behaviors. In addition, the results of this study suggest that eating behaviors and psychological factors should be taken into account in psychological interventions in the treatment of eating disorders. The clinical goal can be considered to be an improvement in non-normative eating behaviors, such as a reduction in overeating episodes or eating less frequently in the absence of a feeling of hunger.

Dynamic relationships among feeling fat, fear of weight gain, and eating disorder symptoms in an eating disorder sample.

Feeling fat and fear of weight gain are key cognitive-affective symptoms that are theorized to maintain eating disorders (EDs). Little research has examined the dynamic relationships among feeling fat, fear of weight gain, emotions, cognitions, and ED behaviors. Furthermore, it is unknown if these relations vary by ED diagnosis (e.g., anorexia nervosa (AN) vs other ED). The current study (N = 94 ED participants; AN n = 64) utilized ecological momentary assessments collected four times a day for 18 days (72 timepoints) asking about feeling fat, fear of weight gain, emotions (i.e., anxiety, guilt), cognitions (i.e., feelings of having overeaten, thoughts about dieting), and ED behaviors (i.e., vomiting, diuretic/laxative use, excessive exercise, body checking, self-weighing, binge-eating, restriction) at stressful timepoints (contemporaneous [mealtime], and prospective/temporal [next-meal]). Multilevel modeling was used to test for between and within-person associations. Higher feeling fat and fear of weight gain independently predicted higher next-meal emotions (i.e., anxiety, guilt), cognitions (i.e., feelings of having overeaten, thoughts about dieting, fear of weight gain, feeling fat), and ED behaviors (i.e., body checking, self-weighing [feeling fat]). There were relationships in the opposite direction, such that some emotions, cognitions, and ED behaviors prospectively predicted feeling fat and fear of weight gain, suggesting existence of a reciprocal cycle. Some differences were found via diagnosis. Findings pinpoint specific dynamic and cyclical relationships among feeling fat, fear of weight gain, and specific ED symptoms, and suggest the need for more research on how feeling fat, fear of weight gain and cognitive-affective-behavioral aspects of ED operate. Future research can test if treatment interventions targeted at feeling fat and fear of weight gain may disrupt these cycles.

POMC-specific knockdown of MeCP2 leads to adverse phenotypes in mice chronically exposed to high fat diet.

Methyl-CpG binding protein 2 (MeCP2) is an epigenetic factor associated with the neurodevelopmental disorders Rett Syndrome and MECP2 duplication syndrome. Previous studies have demonstrated that knocking out MeCP2 globally in the central nervous system leads to an obese phenotype and hyperphagia, however it is not clear if the hyperphagia is the result of an increased preference for food reward or due to an increase in motivation to obtain food reward. We show that mice deficient in MeCP2 specifically in pro-opiomelanocortin (POMC) neurons have an increased preference for high fat diet as measured by conditioned place preference but do not have a greater motivation to obtain food reward using a progressive ratio task, relative to wildtype littermate controls. We also demonstrate that POMC-Cre MeCP2 knockout (KO) mice have increased body weight after long-term high fat diet exposure as well as elevated plasma leptin and corticosterone levels compared to wildtype mice. Taken together, these results are the first to show that POMC-specific loss-of-function Mecp2 mutations leads to dissociable effects on the rewarding/motivational properties of food as well as changes to hormones associated with body weight homeostasis and stress.

A human obesity-associated MC4R mutation with defective Gq/11α signaling leads to hyperphagia in mice.

Melanocortin 4 receptor (MC4R) mutations are the most common cause of human monogenic obesity and are associated with hyperphagia and increased linear growth. While MC4R is known to activate Gsα/cAMP signaling, a substantial proportion of obesity-associated MC4R mutations do not affect MC4R/Gsα signaling. To further explore the role of specific MC4R signaling pathways in the regulation of energy balance, we examined the signaling properties of one such mutant, MC4R (F51L), as well as the metabolic consequences of MC4RF51L mutation in mice. The MC4RF51L mutation produced a specific defect in MC4R/Gq/11α signaling and led to obesity, hyperphagia, and increased linear growth in mice. The ability of a melanocortin agonist to acutely inhibit food intake when delivered to the paraventricular nucleus (PVN) was lost in MC4RF51L mice, as well as in WT mice in which a specific Gq/11α inhibitor was delivered to the PVN; this provided evidence that a Gsα-independent signaling pathway, namely Gq/11α, significantly contributes to the actions of MC4R on food intake and linear growth. These results suggest that a biased MC4R agonist that primarily activates Gq/11α may be a potential agent to treat obesity with limited untoward cardiovascular and other side effects.

Intergenerational inheritance induced by a high-fat diet causes hyperphagia and reduced hypothalamic sensitivity to insulin and leptin in the second-generation of rats.

OBJECTIVE: The aim was to investigate the intergenerational inheritance induced by a high-fat diet on sensitivity to insulin and leptin in the hypothalamic control of satiety in second-generation offspring, which were fed a control diet. METHODS: Progenitor rats were fed a high-fat or a control diet for 59 d until weaning. The first-generation and second-generation offspring were fed the control diet until 90 d of age. Body mass and adiposity index of the progenitors fed the high-fat diet and the second-generation offspring from progenitors fed the high-fat diet were evaluated as were the gene expression of DNA methyltransferase 3a, angiotensin-converting enzyme type 2, angiotensin II type 2 receptor, insulin and leptin signaling pathway (insulin receptor, leptin receptor, insulin receptor substrate 2, protein kinase B, signal transducer and transcriptional activator 3, pro-opiomelanocortin, and neuropeptide Agouti-related protein), superoxide dismutase activity, and the concentration of carbonyl protein and satiety-regulating neuropeptides, pro-opiomelanocortin and neuropeptide Agouti-related protein, in the hypothalamus. RESULTS: The progenitor group fed a high-fat diet showed increased insulin resistance and reduced insulin-secreting beta-cell function and reduced food intake, without changes in caloric intake. The second-generation offspring from progenitors fed a high-fat diet, compared with second-generation offspring from progenitors fed a control diet group, had decreased insulin-secreting beta-cell function and increased food and caloric intake, insulin resistance, body mass, and adiposity index. Furthermore, second-generation offspring from progenitors fed a high-fat diet had increased DNA methyltransferase 3a, neuropeptide Agouti-related protein, angiotensin II type 1 receptor, and nicotinamide adenine dinucleotide phosphate oxidase p47phox gene expression, superoxide dismutase activity, and neuropeptide Agouti-related protein concentration in the hypothalamus. In addition, there were reduced in gene expression of the insulin receptor, leptin receptor, insulin receptor substrate 2, pro-opiomelanocortin, angiotensin II type 2 receptor, angiotensin-converting enzyme type 2, and angiotensin-(1-7) receptor and pro-opiomelanocortin concentration in the second-generation offspring from progenitors fed the high-fat diet. CONCLUSIONS: Overall, progenitors fed a high-fat diet induced changes in the hypothalamic control of satiety of the second-generation offspring from progenitors fed the high-fat diet through intergenerational inheritance. These changes led to hyperphagia, alterations in the hypothalamic pathways of insulin, and leptin and adiposity index increase, favoring the occurrence of different cardiometabolic disorders in the second-generation offspring from progenitors fed the high-fat diet fed only with the control diet.

Intuitive eating and its influence on self-reported weight and eating behaviors.

Intuitive eating (IE) is an adaptive eating behavior that involves paying attention to the body's physiological signals, including eating when hungry and stopping when feeling full. A growing body of literature has examined the effect of IE on the development of maladaptive eating behaviors and body weight, even though IE is not centered around the latter. However, longitudinal observation studies among the general population are still rare. Therefore, this study aimed to longitudinally examine the links between IE and changes in body weight, maladaptive eating behaviors (reward, external, restrained eating), and overeating frequency over time. For this purpose, we used data from the first (2017) and the fourth waves (2020) of the Swiss Food Panel 2.0 survey, which included 1821 randomly selected Swiss participants. The same participants completed a self-administered questionnaire annually, measuring their self-reported eating behaviors and weight status. IE was measured with the Intuitive Eating Scale-2. Results showed that women with high IE scores were more likely to maintain their body weights (within ±2 kg) and less likely to gain weight (>2 kg) than women with low IE scores. No such effects were found for men. Furthermore, IE was linked to a reduction in maladaptive eating behaviors and overeating frequency over time in both genders. Results suggest that IE may counteract maladaptive eating behaviors, which can promote weight stability over time. Therefore, the encouragement of IE patterns seems to be a promising strategy to address problematic eating behaviors and the challenges associated with controlling food intake and prevention of overeating.

Association between dietary diversity, sedentary time outside of work and depressive symptoms among knowledge workers: a multi-center cross-sectional study.

BACKGROUND: Low-diversity diets and sedentary status are risk factors for depressive symptoms, while knowledge workers were ignored before. The purpose of this current study was to examine the relationship between dietary diversity, sedentary time spent outside of work, and depressive symptoms among knowledge workers. STUDY DESIGN AND METHODS: This was a multicenter and cross-sectional design that included 118,723 knowledge workers. Participants self-reported online between January 2018 and December 2020. Demographic information, the Dietary Diversity Scale, the Patient Health Questionnaire-9, dietary habits (which included eating three meals on time, midnight snacking, overeating, social engagement, coffee consumption, sugary drink consumption, smoking and alcohol use), sedentary time spent outside of work and physical activity were investigated. RESULTS: The relationships between demographic information, dietary habits and dietary diversity, and depressive symptoms were estimated. Compared with the first and second levels of dietary diversity, the third level of dietary diversity (OR: 0.91; 95% CI: 0.84-0.98) reduced the risk of depressive symptoms. Knowledge workers with different degrees of sedentary status (2-4 h (OR: 1.11; 95% CI: 1.07-1.14), 4-6 h (OR: 1.21; 95% CI: 1.17-1.26), and > 6 h (OR: 1.49; 95% CI: 1.43-1.56), presented a progressively higher risk of depressive symptoms. CONCLUSION: High amounts of sedentary time spent after work and low levels of dietary diversity are risk factors for depressive symptoms. In addition, an irregular diet and overeating are also major risk factors for knowledge workers.