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Psychiatry and Clinical Neurosciences Jun 2015Sleep-related eating disorder (SRED) is a condition characterized by recurrent episodes of eating at the transition from night-time sleep to arousal. SRED patients... (Review)
Review
Sleep-related eating disorder (SRED) is a condition characterized by recurrent episodes of eating at the transition from night-time sleep to arousal. SRED patients describe eating in an out-of-control manner with preference for high-caloric foods and sometimes with inedible or toxic items. Level of consciousness during SRED episodes ranges from partial consciousness to dense unawareness typical of somnambulistic episodes. SRED is sometimes associated with psychotropic medication, in particular sedative hypnotics, and other sleep disorders, including parasomnias, narcolepsy, and restless legs syndrome. Night eating syndrome (NES) is another important condition in the disordered night-time eating spectrum showing hyperphagia episodes at full arousal from nocturnal sleep without accompanying amnesia. NES could be considered an abnormality in the circadian rhythm of meal timing with a normal circadian timing of sleep onset. The two conditions often overlap and possibly share a common pathophysiology. Studies have suggested that central nervous system serotonin modulation may lead to an effective treatment of NES, while the anti-seizure medication topiramate may be an effective SRED treatment.
Topics: Comorbidity; Feeding and Eating Disorders; Humans; Hyperphagia; Hypnotics and Sedatives; Mental Disorders; Narcolepsy; Parasomnias; Restless Legs Syndrome
PubMed: 25495278
DOI: 10.1111/pcn.12263 -
Molecular Psychiatry May 2023Antipsychotic (AP) drugs are efficacious treatments for various psychiatric disorders, but excessive weight gain and subsequent development of metabolic disease remain... (Review)
Review
Antipsychotic (AP) drugs are efficacious treatments for various psychiatric disorders, but excessive weight gain and subsequent development of metabolic disease remain serious side effects of their use. Increased food intake leads to AP-induced weight gain, but the underlying molecular mechanisms remain unknown. In previous studies, we identified the neuropeptide Agrp and the transcription factor nuclear receptor subfamily 5 group A member 2 (Nr5a2) as significantly upregulated genes in the hypothalamus following AP-induced hyperphagia. While Agrp is expressed specifically in the arcuate nucleus of the hypothalamus and plays a critical role in appetite stimulation, Nr5a2 is expressed in both the CNS and periphery, but its role in food intake behaviors remains unknown. In this study, we investigated the role of hypothalamic Nr5a2 in AP-induced hyperphagia and weight gain. In hypothalamic cell lines, olanzapine treatment resulted in a dose-dependent increase in gene expression of Nr5a2 and Agrp. In mice, the pharmacological inhibition of NR5A2 decreased olanzapine-induced hyperphagia and weight gain, while the knockdown of Nr5a2 in the arcuate nucleus partially reversed olanzapine-induced hyperphagia. Chromatin-immunoprecipitation studies showed for the first time that NR5A2 directly binds to the Agrp promoter region. Lastly, the analysis of single-cell RNA seq data confirms that Nr5a2 and Agrp are co-expressed in a subset of neurons in the arcuate nucleus. In summary, we identify Nr5a2 as a key mechanistic driver of AP-induced food intake. These findings can inform future clinical development of APs that do not activate hyperphagia and weight gain.
Topics: Animals; Humans; Mice; Agouti-Related Protein; Antipsychotic Agents; Eating; Hyperphagia; Hypothalamus; Olanzapine; Receptors, Cytoplasmic and Nuclear; Weight Gain
PubMed: 36765131
DOI: 10.1038/s41380-023-01981-9 -
Nature Communications Nov 2018Palatable foods (fat and sweet) induce hyperphagia, and facilitate the development of obesity. Whether and how overnutrition increases appetite through the...
Palatable foods (fat and sweet) induce hyperphagia, and facilitate the development of obesity. Whether and how overnutrition increases appetite through the adipose-to-brain axis is unclear. O-linked beta-D-N-acetylglucosamine (O-GlcNAc) transferase (OGT) couples nutrient cues to O-GlcNAcylation of intracellular proteins at serine/threonine residues. Chronic dysregulation of O-GlcNAc signaling contributes to metabolic diseases. Here we show that adipocyte OGT is essential for high fat diet-induced hyperphagia, but is dispensable for baseline food intake. Adipocyte OGT stimulates hyperphagia by transcriptional activation of de novo lipid desaturation and accumulation of N-arachidonyl ethanolamine (AEA), an endogenous appetite-inducing cannabinoid (CB). Pharmacological manipulation of peripheral CB1 signaling regulates hyperphagia in an adipocyte OGT-dependent manner. These findings define adipocyte OGT as a fat sensor that regulates peripheral lipid signals, and uncover an unexpected adipose-to-brain axis to induce hyperphagia and obesity.
Topics: Acetylglucosamine; Adipocytes; Adipose Tissue; Animals; Blotting, Western; Body Weight; Cannabinoids; Cell Line; Humans; Hyperphagia; In Vitro Techniques; Male; Mice; Mice, Inbred C57BL; Obesity; Real-Time Polymerase Chain Reaction
PubMed: 30504766
DOI: 10.1038/s41467-018-07461-x -
Appetite Jun 2009To examine the literature on binge eating to gain a better understanding of its biological foundations and their role in eating disorders. (Review)
Review
OBJECTIVE
To examine the literature on binge eating to gain a better understanding of its biological foundations and their role in eating disorders.
METHOD
Literature review and synthesis.
RESULTS
Research using animal models has revealed several factors that contribute to the development and maintenance of binge eating. These factors, including stress, food restriction, the presence of palatable foods, and environmental conditioning, parallel many of the precursory circumstances leading to binge eating in individuals with bulimia nervosa and binge eating disorder.
DISCUSSION
The animal literature has opened a new avenue to aid in the understanding of the neurobiological basis of binge eating. Future endeavors examining the genetic and environmental correlates of binge eating behavior will further contribute to the understanding of the biological foundations of binge eating and assist with establishing diagnostic criteria and the development of novel treatments for eating disorders marked by binge eating.
Topics: Analgesics, Opioid; Animals; Behavior, Addictive; Bulimia; Bulimia Nervosa; Disease Models, Animal; Dopamine; Environment; Food Deprivation; Food Preferences; Humans; Hyperphagia; Stress, Psychological; Taste
PubMed: 19501749
DOI: 10.1016/j.appet.2009.03.005 -
The Proceedings of the Nutrition Society Aug 2018Offering large portions of high-energy-dense (HED) foods increases overall intake in children and adults. This is known as the portion size effect (PSE). It is robust,... (Review)
Review
Offering large portions of high-energy-dense (HED) foods increases overall intake in children and adults. This is known as the portion size effect (PSE). It is robust, reliable and enduring. Over time, the PSE may facilitate overeating and ultimately positive energy balance. Therefore, it is important to understand what drives the PSE and what might be done to counter the effects of an environment promoting large portions, especially in children. Explanations for the PSE are many and diverse, ranging from consumer error in estimating portion size to simple heuristics such as cleaning the plate or eating in accordance with consumption norms. However, individual characteristics and hedonic processes influence the PSE, suggesting a more complex explanation than error or heuristics. Here PSE studies are reviewed to identify interventions that can be used to downsize portions of HED foods, with a focus on children who are still learning about social norms for portion size. Although the scientific evidence for the PSE is robust, there is still a need for creative downsizing solutions to facilitate portion control as children and adolescents establish their eating habits.
Topics: Child; Child Development; Eating; Energy Intake; Feeding Behavior; Humans; Hyperphagia; Individuality; Learning; Obesity; Pleasure; Portion Size; Satiation
PubMed: 29792243
DOI: 10.1017/S0029665118000435 -
Philosophical Transactions of the Royal... Jul 2006The brain-gut peptide cholecystokinin (CCK) inhibits food intake following peripheral or site directed central administration. Peripheral exogenous CCK inhibits food... (Review)
Review
The brain-gut peptide cholecystokinin (CCK) inhibits food intake following peripheral or site directed central administration. Peripheral exogenous CCK inhibits food intake by reducing the size and duration of a meal. Antagonist studies have demonstrated that the actions of the exogenous peptide mimic those of endogenous CCK. Antagonist administration results in increased meal size and meal duration. The feeding inhibitory actions of CCK are mediated through interactions with CCK-1 receptors. The recent identification of the Otsuka-Long-Evans-Tokushima Fatty (OLETF) rat as a spontaneous CCK-1 receptor knockout model has allowed a more comprehensive evaluation of the feeding actions of CCK. OLETF rats become obese and develop non-insulin dependent diabetes mellitus (NIDDM). Consistent with the absence of CCK-1 receptors, OLETF rats do not respond to exogenous CCK. OLETF rats are hyperphagic and their increased food intake is characterized by a large increase in meal size with a decrease in meal frequency that is not sufficient to compensate for the meal size increase. Deficits in meal size control are evident in OLETF rats as young as 2 days of age. OLETF obesity is secondary to the increased food intake. Pair feeding to amounts consumed by intact control rats normalizes body weight, body fat and elevated insulin and glucose levels. Hypothalamic arcuate nucleus peptide mRNA expression in OLETF rats is appropriate to their obesity and is normalized by pair feeding. In contrast, pair fed and young pre-obese OLETF rats have greatly elevated dorsomedial hypothalamic (DMH) neuropeptide Y (NPY) mRNA expression. Elevated DMH NPY in OLETF rats appears to be a consequence of the absence of CCK-1 receptors. In intact rats NPY and CCK-1 receptors colocalize to neurons within the compact subregion of the DMH and local CCK administration reduces food intake and decreases DMH NPY mRNA expression. We have proposed that the absence of DMH CCK-1 receptors significantly contributes to the OLETF's inability to compensate for their meal size control deficit leading to their overall hyperphagia. Access to a running wheel and the resulting exercise normalizes food intake and body weight in OLETF rats. When given access to running wheels for 6 weeks shortly after weaning, OLETF rats do not gain weight to the same degree as sedentary OLETF rats and do not develop NIDDM. Exercise also prevents elevated levels of DMH NPY mRNA expression, suggesting that exercise exerts an alternative, non-CCK mediated, control on DMH NPY. The OLETF rat is a valuable model for characterizing actions of CCK in energy balance and has provided novel insights into interactions between exercise and food intake.
Topics: Animals; Feeding Behavior; Hyperphagia; Obesity; Rats; Rats, Inbred OLETF; Receptors, Cholecystokinin
PubMed: 16815799
DOI: 10.1098/rstb.2006.1857 -
Neuropsychopharmacology : Official... Jun 2017Compulsive eating behavior is a transdiagnostic construct that is characteristic of medical and psychiatric conditions such as forms of obesity and eating disorders.... (Review)
Review
Compulsive eating behavior is a transdiagnostic construct that is characteristic of medical and psychiatric conditions such as forms of obesity and eating disorders. Although feeding research is moving toward a better understanding of the proposed addictive properties of food, the components and the mechanisms contributing to compulsive eating are not yet clearly defined or understood. Current understanding highlights three elements of compulsive behavior as it applies to pathological overeating: (1) habitual overeating; (2) overeating to relieve a negative emotional state; and (3) overeating despite aversive consequences. These elements emerge through mechanisms involving pathological habit formation through an aberrant learning process, the emergence of a negative emotional state, and dysfunctions in behavioral control. Dysfunctions in systems within neurocircuitries that comprise the basal ganglia, the extended amygdala, and the prefrontal cortex result in compulsive eating behaviors. Here, we present evidence to relate compulsive eating behavior and addiction and to characterize their underlying neurobiological mechanisms. A major need to improve understanding of compulsive eating through the integration of complex motivational, emotional, and cognitive constructs is warranted.
Topics: Amygdala; Behavior, Addictive; Compulsive Behavior; Humans; Hyperphagia; Nerve Net; Prefrontal Cortex
PubMed: 27922596
DOI: 10.1038/npp.2016.269 -
Cell Reports Feb 2020The vagus nerve conveys gastrointestinal cues to the brain to control eating behavior. In obesity, vagally mediated gut-brain signaling is disrupted. Here, we show that...
The vagus nerve conveys gastrointestinal cues to the brain to control eating behavior. In obesity, vagally mediated gut-brain signaling is disrupted. Here, we show that the cocaine- and amphetamine-regulated transcript (CART) is a neuropeptide synthesized proportional to the food consumed in vagal afferent neurons (VANs) of chow-fed rats. CART injection into the nucleus tractus solitarii (NTS), the site of vagal afferent central termination, reduces food intake. Conversely, blocking endogenous CART action in the NTS increases food intake in chow-fed rats, and this requires intact VANs. Viral-mediated Cartpt knockdown in VANs increases weight gain and daily food intake via larger meals and faster ingestion rate. In obese rats fed a high-fat, high-sugar diet, meal-induced CART synthesis in VANs is blunted and CART antibody fails to increase food intake. However, CART injection into the NTS retains its anorexigenic effect in obese rats. Restoring disrupted VAN CART signaling in obesity could be a promising therapeutic approach.
Topics: Animals; Humans; Hyperphagia; Male; Nerve Tissue Proteins; Rats; Vagus Nerve; Weight Gain
PubMed: 32049029
DOI: 10.1016/j.celrep.2020.01.045 -
Pediatric Obesity Nov 2022Children with Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) have an increased obesity risk. Although these conditions commonly...
BACKGROUND
Children with Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) have an increased obesity risk. Although these conditions commonly co-occur, shared factors relating to obesity risk are unknown.
OBJECTIVES
To examine the shared and unique associations of ADHD and autistic traits with eating behaviours and BMI.
METHODS
Children (N = 4134) from the population-based Generation R Study were categorized into subgroups based on parent-reported ADHD and autistic traits scores at 6 years: ADHD , ASD , ADHD+ASD and REF (reference group: ADHD+ASD ). Multiple linear regressions examined the associations between subgroups and eating behaviours (at 10 years) and BMIz (at 14 years), relative to REF. Mediation analyses tested the indirect effect of subgroup and BMIz through eating behaviours.
RESULTS
ADHD + ASD children expressed both food approach (increased food responsiveness and emotional overeating) and avoidant eating behaviours (increased emotional undereating, satiety responsiveness/ slowness in eating and picky eating, and decreased enjoyment in food). ASD children were more food avoidant, while ADHD children had more food approach behaviours and greater BMIz. ADHD and BMIz were indirectly associated with food responsiveness and emotional overeating.
CONCLUSIONS
ADHD and autistic trait phenotypes show distinct associations with potential obesity risk factors, and further research is needed to improve targeted early intervention.
Topics: Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Autistic Disorder; Feeding Behavior; Humans; Hyperphagia; Obesity
PubMed: 35751176
DOI: 10.1111/ijpo.12951 -
Orphanet Journal of Rare Diseases Jul 2023Bardet-Biedl syndrome (BBS) is a rare, genetically heterogeneous obesity syndrome associated with hyperphagia. Given the early onset of BBS symptoms in childhood and...
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.
Topics: Humans; Adult; Child; Bardet-Biedl Syndrome; Caregiver Burden; Cross-Sectional Studies; Obesity; Hyperphagia; Surveys and Questionnaires
PubMed: 37415214
DOI: 10.1186/s13023-023-02692-8