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Endocrinology Aug 2020Obesity is a chronic recurring disease whose prevalence has almost tripled over the past 40 years. In individuals with obesity, there is significant increased risk of... (Review)
Review
Obesity is a chronic recurring disease whose prevalence has almost tripled over the past 40 years. In individuals with obesity, there is significant increased risk of morbidity and mortality, along with decreased quality of life. Increased obesity prevalence results, at least partly, from the increased global food supply that provides ubiquitous access to tasty, energy-dense foods. These hedonic foods and the nonfood cues that through association become reward predictive cues activate brain appetitive control circuits that drive hyperphagia and weight gain by enhancing food-seeking, motivation, and reward. Behavioral therapy (diet and lifestyle modifications) is the recommended initial treatment for obesity, yet it often fails to achieve meaningful weight loss. Furthermore, those who lose weight regain it over time through biological regulation. The need to effectively treat the pathophysiology of obesity thus centers on biologically based approaches such as bariatric surgery and more recently developed drug therapies. This review highlights neurobiological aspects relevant to obesity causation and treatment by emphasizing the common aspects of the feeding-inhibitory effects of multiple signals. We focus on glucagon like peptide-1 receptor (GLP-1R) signaling as a promising obesity treatment target by discussing the activation of intestinal- and brain-derived GLP-1 and GLP-1R expressing central nervous system circuits resulting from normal eating, bariatric surgery, and GLP-1R agonist drug therapy. Given the increased availability of energy-dense foods and frequent encounters with cues that drive hyperphagia, this review also describes how bariatric surgery and GLP-1R agonist therapies influence food reward and the motivational drive to overeat.
Topics: Animals; Bariatric Surgery; Behavior Therapy; Eating; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Hyperphagia; Obesity; Receptors, Glucagon; Weight Loss
PubMed: 32516384
DOI: 10.1210/endocr/bqaa093 -
International Journal of Molecular... Jan 2023Prader-Willi syndrome (PWS) is a complex, genetic, neurodevelopmental disorder. PWS has three molecular genetic classes. The most common defect is due to a paternal... (Review)
Review
Prader-Willi syndrome (PWS) is a complex, genetic, neurodevelopmental disorder. PWS has three molecular genetic classes. The most common defect is due to a paternal 15q11-q13 deletion observed in about 60% of individuals. This is followed by maternal disomy 15 (both 15 s from the mother), found in approximately 35% of cases. the remaining individuals have a defect of the imprinting center that controls the activity of imprinted genes on chromosome 15. Mild cognitive impairment and behavior problems in PWS include self-injury, anxiety, compulsions, and outbursts in childhood, impacted by genetic subtypes. Food seeking and hyperphagia can lead to morbid obesity and contribute to diabetes and cardiovascular or orthopedic problems. The control of hyperphagia and improving food-related behaviors are the most important unmet needs in PWS and could be addressed with the development of a new therapeutic agent, as currently no approved therapeutics exist for PWS treatment. The status of clinical trials with existing results for the management of obesity and hyperphagia in PWS will be discussed in this review, including treatments such as beloranib, setmelanotide, a diazoxide choline controlled-release tablet (DCCR), an unacylated ghrelin analogue, oxytocin and related compounds, glucagon-like peptide 1 receptor agonists, surgical intervention, and transcranial direct-current stimulation.
Topics: Female; Humans; Prader-Willi Syndrome; Transcranial Direct Current Stimulation; Hyperphagia; Anxiety; Mothers
PubMed: 36768472
DOI: 10.3390/ijms24032150 -
Nutrients May 2022Prader-Willi syndrome (PWS) is a complex genetic disorder which involves the endocrine and neurologic systems, metabolism, and behavior. The aim of this paper is to... (Review)
Review
Prader-Willi syndrome (PWS) is a complex genetic disorder which involves the endocrine and neurologic systems, metabolism, and behavior. The aim of this paper is to summarize current knowledge on dietary management and treatment of PWS and, in particular, to prevent excessive weight gain. Growth hormone (GH) therapy is the recommended standard treatment for PWS children, because it improves body composition (by changing the proportion of body fat and lean body mass specifically by increasing muscle mass and energy expenditure), linear growth, and in infants, it promotes psychomotor and IQ development. In early childhood, the predominant symptom is hyperphagia which can lead to early onset, severe obesity with different obesity-related comorbidities. There are several studies on anti-obesity medications (metformin, topiramate, liraglutide, setmelanotide). However, these are still limited, and no widely accepted consensus guideline exists concerning these drugs in children with PWS. Until there is a specific treatment for hyperphagia and weight gain, weight must be controlled with the help of diet and exercise. Below the age of one year, children with PWS have no desire to eat and will often fail to thrive, despite adequate calories. After the age of two years, weight begins to increase without a change in calorie intake. Appetite increases later, gradually, and becomes insatiable. Managing the progression of different nutritional phases (0-4) is really important and can delay the early onset of severe obesity. Multidisciplinary approaches are crucial in the diagnosis and lifelong follow-up, which will determine the quality of life of these patients.
Topics: Child; Child, Preschool; Humans; Hyperphagia; Infant; Obesity, Morbid; Prader-Willi Syndrome; Quality of Life; Weight Gain
PubMed: 35565916
DOI: 10.3390/nu14091950 -
Psychiatry Research Dec 2014This study sought to examine risk and onset patterns in anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). Women with AN (n=71), BN (n=66),...
This study sought to examine risk and onset patterns in anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). Women with AN (n=71), BN (n=66), BED (n=160) and non-psychiatric controls (n=323) were compared retrospectively on risk factors, symptom onset, and diagnostic migration. Eating disorder groups reported greater risk exposure than non-psychiatric controls. AN and BED differed on premorbid personality/behavioral problems, childhood obesity, and family overeating. Risk factors for BN were shared with AN and BED. Dieting was the most common onset symptom in AN, whereas binge eating was most common in BN and BED. Migration between AN and BED was rare, but more frequent between AN and BN and between BN and BED. AN and BED have distinct risk factors and onset patterns, while BN shares similar risk factors and onset patterns with both AN and BED. Results should inform future classification schemes and prevention programs.
Topics: Adult; Anorexia Nervosa; Binge-Eating Disorder; Case-Control Studies; Feeding and Eating Disorders; Female; Humans; Hyperphagia; Overweight; Personality Disorders; Retrospective Studies; Risk Factors; Young Adult
PubMed: 25103674
DOI: 10.1016/j.psychres.2014.05.054 -
Nature Reviews. Endocrinology Aug 2017The concept of addiction is loaded with connotations and is often used for its political as much as its medical utility. The scientific case for 'food addiction' as a... (Review)
Review
The concept of addiction is loaded with connotations and is often used for its political as much as its medical utility. The scientific case for 'food addiction' as a clinical phenotype currently rests on its association with generic diagnostic criteria for substance-related disorders being applied to everyday foods and eating-related problems. This has fused the concept of obesity with addiction regardless of whether it fits the definition. The hedonic, or reward, system can account for the ingestion of foods and drugs, confirming that they share neural substrates that differentiate liking and wanting. These are normal processes that are recruited for natural homeostatic behaviours and can explain the phenomenon of hedonic overeating as a consequence of human motivation pushed to extremes by an obesogenic environment. Food addiction constitutes a medicalization of common eating behaviours, taking on the properties of a disease. The use of this medical language has implications for the way in which society views overeating and obesity.
Topics: Animals; Behavior, Addictive; Feeding Behavior; Humans; Hyperphagia; Medicalization; Obesity; Philosophy
PubMed: 28549063
DOI: 10.1038/nrendo.2017.61 -
Nutrients Sep 2019With the obesity epidemic being largely attributed to overeating, much research has been aimed at understanding the psychological causes of overeating and using this... (Review)
Review
With the obesity epidemic being largely attributed to overeating, much research has been aimed at understanding the psychological causes of overeating and using this knowledge to develop targeted interventions. Here, we review this literature under a model of food addiction and present evidence according to the fifth edition of the Diagnostic and Statistical Manual (DSM-5) criteria for substance use disorders. We review several innovative treatments related to a food addiction model ranging from cognitive intervention tasks to neuromodulation techniques. We conclude that there is evidence to suggest that, for some individuals, food can induce addictive-type behaviours similar to those seen with other addictive substances. However, with several DSM-5 criteria having limited application to overeating, the term 'food addiction' is likely to apply only in a minority of cases. Nevertheless, research investigating the underlying psychological causes of overeating within the context of food addiction has led to some novel and potentially effective interventions. Understanding the similarities and differences between the addictive characteristics of food and illicit substances should prove fruitful in further developing these interventions.
Topics: Food Addiction; Humans; Hyperphagia
PubMed: 31487791
DOI: 10.3390/nu11092086 -
The Journal of Clinical Endocrinology... Jun 2023Prader-Willi syndrome (PWS) is a rare neurobehavioral-metabolic disease caused by the lack of paternally expressed genes in the chromosome 15q11-q13 region,... (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
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 not controlled.
OBJECTIVE
The primary end point was change from baseline in hyperphagia using the Hyperphagia Questionnaire for Clinical Trials (HQ-CT). Other end points included Global Impression Scores, and changes in body composition, behaviors, and hormones.
METHODS
In DESTINY PWS, a 13-week, randomized, double-blind, placebo-controlled, phase 3 trial, 127 participants with PWS aged 4 years and older with hyperphagia were randomly assigned 2:1 to diazoxide choline extended-release tablet (DCCR) or placebo.
RESULTS
DCCR did not significantly improve hyperphagia (HQ-CT least-square mean (LSmean) [SE] -5.94 [0.879] vs -4.27 [1.145]; P = .198), but did so in participants with severe hyperphagia (LSmean [SE] -9.67 [1.429] vs -4.26 [1.896]; P = .012). Two of 3 secondary end points were improved (Clinical Global Impression of Improvement [CGI-I]; P = .029; fat mass; P = .023). In an analysis of results generated pre-COVID, the primary (HQ-CT; P = .037) and secondary end points were all improved (CGI-I; P = .015; Caregiver Global Impression of Change; P = .031; fat mass; P = .003). In general, DCCR was well tolerated with 83.3% in the DCCR group experiencing a treatment-emergent adverse event and 73.8% in the placebo group (not significant).
CONCLUSION
DCCR did not significantly improve hyperphagia in the primary analysis but did in participants with severe baseline hyperphagia and in the pre-COVID analysis. DCCR treatment was associated with significant improvements in body composition and clinician-reported outcomes.
Topics: Humans; Prader-Willi Syndrome; Diazoxide; COVID-19; Obesity; Hyperphagia
PubMed: 36639249
DOI: 10.1210/clinem/dgad014 -
Pediatric Obesity Jan 2018Obesity is the most common cause of metabolic complications and poor quality of life in Prader-Willi syndrome (PWS). Hyperphagia and obesity develop after an initial... (Review)
Review
Obesity is the most common cause of metabolic complications and poor quality of life in Prader-Willi syndrome (PWS). Hyperphagia and obesity develop after an initial phase of poor feeding and failure to thrive. Several mechanisms for the aetiology of obesity in PWS are proposed, which include disruption in hypothalamic pathways of satiety control resulting in hyperphagia, aberration in hormones regulating food intake, reduced energy expenditure because of hypotonia and altered behaviour with features of autism spectrum disorder. Profound muscular hypotonia prevents PWS patients from becoming physically active, causing reduced muscle movements and hence reduced energy expenditure. In a quest for the aetiology of obesity, recent evidence has focused on several appetite-regulating hormones, growth hormone, thyroid hormones and plasma adipocytokines. However, despite advancement in understanding of the genetic basis of PWS, there are contradictory data on the role of satiety hormones in hyperphagia and data regarding dietary intake are limited. Mechanistic studies on the aetiology of obesity and its relationship with disease pathogenesis in PWS are required. . In this review, we focused on the available evidence regarding mechanisms of obesity and potential new areas that could be explored to help unravel obesity pathogenesis in PWS.
Topics: Appetite; Child; Child, Preschool; Eating; Humans; Hyperphagia; Obesity; Prader-Willi Syndrome; Quality of Life
PubMed: 27863129
DOI: 10.1111/ijpo.12177 -
Eating and Weight Disorders : EWD Jun 2020Emotional eating is important to study and address because it predicts poor outcome in weight loss interventions. Interventions have only touched the surface in terms of...
PURPOSE
Emotional eating is important to study and address because it predicts poor outcome in weight loss interventions. Interventions have only touched the surface in terms of addressing emotional eating. Mindfulness approaches can address emotional eating by modification of emotion regulation and appetitive traits. The current study involved development of an emotional eating-specific mindfulness intervention and assessment of its effect on appetitive traits associated with emotional eating.
METHODS
Participants (n = 14; age M = 29 years; 90% female) completed baseline and end-of-intervention self-report measures of emotional eating, food-cue reactivity, mindfulness, intuitive eating, emotional impulse regulation, stress, and a behavioural measure of inhibitory control. During the 6-week intervention, mindfulness meditation skills were taught weekly embedded in a psycho-educational curriculum about emotional eating.
RESULTS
Paired t tests, controlled for type 1 error, revealed significant improvements in food-cue reactivity, intuitive eating, emotional impulse regulation, inhibitory control and stress (ps < 0.05; d: 0.58-1.54). Changes in emotional eating approached significance (p = 0.075, d = 0.66).
CONCLUSION
The intervention purposefully did not focus on weight loss and recruited participants who had self-declared difficulties with emotional eating. The positive outcomes suggest that intervening with mindfulness training before weight loss is attempted has the potential to change psychological factors that underpin overeating and undermine weight loss efforts. The study provides proof of principle as a basis to design a randomized control trial to assess rigorously the effectiveness of the intervention as a precursor to a weight loss intervention.
LEVEL OF EVIDENCE
Level IV, uncontrolled trial.
Topics: Adult; Eating; Emotions; Feeding Behavior; Female; Humans; Hyperphagia; Male; Mindfulness; Obesity; Overweight
PubMed: 30859465
DOI: 10.1007/s40519-019-00667-y -
Cell Metabolism Feb 2024Food is a powerful natural reinforcer that guides feeding decisions. The vagus nerve conveys internal sensory information from the gut to the brain about nutritional...
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.
Topics: Humans; Sugars; Carbohydrates; Brain; Diet; Hyperphagia
PubMed: 38242133
DOI: 10.1016/j.cmet.2023.12.014