-
Psychopharmacology Jun 2023Nicotine cessation is associated with increased consumption of highly palatable foods and body weight gain in most smokers. Concerns about body weight gain are a major...
RATIONALE
Nicotine cessation is associated with increased consumption of highly palatable foods and body weight gain in most smokers. Concerns about body weight gain are a major barrier to maintaining long-term smoking abstinence, and current treatments for nicotine use disorder (NUD) delay, but do not prevent, body weight gain during abstinence. Glucagon-like peptide-1 receptor (GLP-1R) agonists reduce food intake and are FDA-approved for treating obesity. However, the effects of GLP-1R agonist monotherapy on nicotine seeking and withdrawal-induced hyperphagia are unknown.
OBJECTIVES
We screened the efficacy of the long-lasting GLP-1R agonist liraglutide to reduce nicotine-mediated behaviors including voluntary nicotine taking, as well as nicotine seeking and hyperphagia during withdrawal.
METHODS
Male and female rats self-administered intravenous nicotine (0.03 mg/kg/inf) for ~21 days. Daily liraglutide administration (25 μg/kg, i.p.) started on the last self-administration day and continued throughout the extinction and reinstatement phases of the experiment. Once nicotine taking was extinguished, the reinstatement of nicotine-seeking behavior was assessed after an acute priming injection of nicotine (0.2 mg/kg, s.c.) and re-exposure to conditioned light cues. Using a novel model of nicotine withdrawal-induced hyperphagia, intake of a high fat diet (HFD) was measured during home cage abstinence in male and female rats with a history of nicotine self-administration.
RESULTS
Liraglutide attenuated nicotine self-administration and reinstatement in male and female rats. Repeated liraglutide attenuated withdrawal-induced hyperphagia and body weight gain in male and female rats at a dose that was not associated with malaise-like effects.
CONCLUSIONS
These findings support further studies investigating the translational potential of GLP-1R agonists to treat NUD.
Topics: Female; Rats; Male; Animals; Nicotine; Liraglutide; Tobacco Use Disorder; Obesity; Hyperphagia; Self Administration; Extinction, Psychological
PubMed: 37129617
DOI: 10.1007/s00213-023-06376-w -
Obesity (Silver Spring, Md.) Feb 2014Hyperphagia is a central feature of inherited disorders (e.g., Prader-Willi Syndrome) in which obesity is a primary phenotypic component. Hyperphagia may also contribute...
OBJECTIVE
Hyperphagia is a central feature of inherited disorders (e.g., Prader-Willi Syndrome) in which obesity is a primary phenotypic component. Hyperphagia may also contribute to obesity as observed in the general population, thus raising the potential importance of common underlying mechanisms and treatments. Substantial gaps in understanding the molecular basis of inherited hyperphagia syndromes are present as are a lack of mechanistic of mechanistic targets that can serve as a basis for pharmacologic and behavioral treatments.
DESIGN AND METHODS
International conference with 28 experts, including scientists and caregivers, providing presentations, panel discussions, and debates.
RESULTS
The reviewed collective research and clinical experience provides a critical body of new and novel information on hyperphagia at levels ranging from molecular to population. Gaps in understanding and tools needed for additional research were identified.
CONCLUSIONS
This report documents the full scope of important topics reviewed at a comprehensive international meeting devoted to the topic of hyperphagia and identifies key areas for future funding and research.
Topics: Basic Helix-Loop-Helix Transcription Factors; Behavior, Addictive; Craniopharyngioma; Eating; Feeding Behavior; Female; Humans; Hyperphagia; Male; Models, Animal; Obesity; Odds Ratio; Phenotype; Prader-Willi Syndrome; Repressor Proteins; Research; Satiety Response
PubMed: 24574081
DOI: 10.1002/oby.20646 -
Obesity Research Nov 2001Overeating is a relative term. It refers to the consumption of an energy intake that is inappropriately large for a given energy expenditure, thus, leading to obesity.... (Review)
Review
Overeating is a relative term. It refers to the consumption of an energy intake that is inappropriately large for a given energy expenditure, thus, leading to obesity. There are several key environmental and cultural factors that have converged in the past few decades to markedly increase the risk of both active and passive (inadvertent) overeating. Chief among these are the increased availability and promotion of cheap energy-dense diets (usually high in fat) and the transition toward extremely sedentary lifestyles. The importance of considering these factors together must be stressed. Data ranging from highly controlled metabolic studies to large-scale epidemiological and ecological analysis illustrate the strong interactions between diet and physical activity in relationship to the over-consumption of energy. Overeating of certain specific dietary components may also lead to health risks. Obvious examples are saturated and trans-fatty acids. More recently attention has switched to high glycemic foods and to n-6 fatty acids. Theories that excess consumption of these may be independent risk factors for obesity and ill health remain controversial but merit closer examination and additional research. The main barriers to changing widely prevalent overeating include the following: public and corporate ignorance about the effects of energy-dense diets in inducing passive over-consumption, commercial willfulness concerning energy density and portion sizes, and public ignorance about the profound health effects of inactive lifestyles. These represent key targets for the design of public health initiatives.
Topics: Animals; Dietary Carbohydrates; Dietary Fats; Energy Intake; Energy Metabolism; Exercise; Female; Food Industry; Humans; Hyperphagia; Male; Risk Factors
PubMed: 11707547
DOI: 10.1038/oby.2001.124 -
Orphanet Journal of Rare Diseases Feb 2024The 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...
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.
Topics: Child; Female; Humans; Infant; Child, Preschool; Hyperphagia; Obesity; Body Mass Index; Feeding Behavior; Impulsive Behavior; Surveys and Questionnaires
PubMed: 38395939
DOI: 10.1186/s13023-024-03085-1 -
The Journal of Physiology Oct 2016This review highlights evidence for a role of the vagus nerve in the development of obesity and how targeting the vagus nerve with neuromodulation or pharmacology can be... (Review)
Review
This review highlights evidence for a role of the vagus nerve in the development of obesity and how targeting the vagus nerve with neuromodulation or pharmacology can be used as a therapeutic treatment of obesity. The vagus nerve innervating the gut plays an important role in controlling metabolism. It communicates peripheral information about the volume and type of nutrients between the gut and the brain. Depending on the nutritional status, vagal afferent neurons express two different neurochemical phenotypes that can inhibit or stimulate food intake. Chronic ingestion of calorie-rich diets reduces sensitivity of vagal afferent neurons to peripheral signals and their constitutive expression of orexigenic receptors and neuropeptides. This disruption of vagal afferent signalling is sufficient to drive hyperphagia and obesity. Furthermore neuromodulation of the vagus nerve can be used in the treatment of obesity. Although the mechanisms are poorly understood, vagal nerve stimulation prevents weight gain in response to a high-fat diet. In small clinical studies, in patients with depression or epilepsy, vagal nerve stimulation has been demonstrated to promote weight loss. Vagal blockade, which inhibits the vagus nerve, results in significant weight loss. Vagal blockade is proposed to inhibit aberrant orexigenic signals arising in obesity as a putative mechanism of vagal blockade-induced weight loss. Approaches and molecular targets to develop future pharmacotherapy targeted to the vagus nerve for the treatment of obesity are proposed. In conclusion there is strong evidence that the vagus nerve is involved in the development of obesity and it is proving to be an attractive target for the treatment of obesity.
Topics: Animals; Body Weight; Diet, High-Fat; Humans; Hyperphagia; Neurons, Afferent; Obesity; Vagus Nerve
PubMed: 26959077
DOI: 10.1113/JP271538 -
European Journal of Medical Genetics Jan 2022Prader-Willi Syndrome (PWS) is a multi-system genetically determined neurodevelopmental disorder and the commonest cause of syndromal obesity. The development of... (Meta-Analysis)
Meta-Analysis
Prader-Willi Syndrome (PWS) is a multi-system genetically determined neurodevelopmental disorder and the commonest cause of syndromal obesity. The development of hyperphagia in early childhood is part of the phenotype arising as a result of an impaired neural response to food intake and the inability to regulate food intake in line with energy needs. Severe obesity develops if access to food is not controlled. In this review we evaluate the evidence for increased morbidity and mortality in PWS in order to establish the extent to which it is directly related to the obesity; a consequence of the eating behaviour itself independent of obesity; or associated with other characteristics of the syndrome. Medline, Cochrane, PsychINFO, CINAHL, Web of Science and Scopus databases were used to systematically identify published material on PWS and hyperphagia and syndrome-related morbidity and mortality. One hundred and ten key papers were selected. Data on 500 people with PWS indicated that the average age of death was 21 years and obesity was, as expected, a significant factor. However, the behaviour of hyperphagia itself, independent of obesity, was also important, associated with choking, gastric rupture, and/or respiratory illness. Other syndrome-related factors increased the risk for, and seriousness of, co-morbid illness or accidents. We conclude that improving life-expectancy largely depends on managing the immediate non-obesity and obesity-related consequences of the hyperphagia, through improved support. The development of new treatments that significantly reduce the drive to eat are likely to decrease morbidity and mortality improving quality of life and life expectancy.
Topics: Humans; Hyperphagia; Morbidity; Prader-Willi Syndrome
PubMed: 34748997
DOI: 10.1016/j.ejmg.2021.104379 -
Obesity Facts 2012The dramatically increasing prevalence of obesity, associated with potentially life-threatening health problems, including cardiovascular diseases and type II diabetes,... (Review)
Review
The dramatically increasing prevalence of obesity, associated with potentially life-threatening health problems, including cardiovascular diseases and type II diabetes, poses an enormous public health problem. It has been proposed that the obesity epidemic can be explained by the concept of 'food addiction'. In this review we focus on possible similarities between binge eating disorder (BED), which is highly prevalent in the obese population, and drug addiction. Indeed, both behavioral and neural similarities between addiction and BED have been demonstrated. Behavioral similarities are reflected in the overlap in DSM-IV criteria for drug addiction with the (suggested) criteria for BED and by food addiction-like behavior in animals after prolonged intermittent access to palatable food. Neural similarities include the overlap in brain regions involved in food and drug craving. Decreased dopamine D2 receptor availability in the striatum has been found in animal models of binge eating, after cocaine self-administration in animals as well as in drug addiction and obesity in humans. To further explore the neurobiological basis of food addiction, it is essential to have an animal model to test the addictive potential of palatable food. A recently developed animal model for drug addiction involves three behavioral characteristics that are based on the DSM-IV criteria: i) extremely high motivation to obtain the drug, ii) difficulty in limiting drug seeking even in periods of explicit non-availability, iii) continuation of drug-seeking despite negative consequences. Indeed, it has been shown that a subgroup of rats, after prolonged cocaine self-administration, scores positive on these three criteria. If food possesses addictive properties, then food-addicted rats should also meet these criteria while searching for and consuming food. In this review we discuss evidence from literature regarding food addiction-like behavior. We also suggest future experiments that could further contribute to our understanding of behavioral and neural commonalities and differences between obesity and drug addiction.
Topics: Animals; Behavior, Addictive; Binge-Eating Disorder; Bulimia; Disease Models, Animal; Eating; Feeding Behavior; Food; Humans; Hyperphagia; Obesity; Substance-Related Disorders
PubMed: 22647301
DOI: 10.1159/000338292 -
Cell Reports Jun 2021Hepatic lipid accumulation is a hallmark of type II diabetes (T2D) associated with hyperinsulinemia, insulin resistance, and hyperphagia. Hepatic synthesis of GABA,... (Clinical Trial)
Clinical Trial
Hepatic lipid accumulation is a hallmark of type II diabetes (T2D) associated with hyperinsulinemia, insulin resistance, and hyperphagia. Hepatic synthesis of GABA, catalyzed by GABA-transaminase (GABA-T), is upregulated in obese mice. To assess the role of hepatic GABA production in obesity-induced metabolic and energy dysregulation, we treated mice with two pharmacologic GABA-T inhibitors and knocked down hepatic GABA-T expression using an antisense oligonucleotide. Hepatic GABA-T inhibition and knockdown decreased basal hyperinsulinemia and hyperglycemia and improved glucose intolerance. GABA-T knockdown improved insulin sensitivity assessed by hyperinsulinemic-euglycemic clamps in obese mice. Hepatic GABA-T knockdown also decreased food intake and induced weight loss without altering energy expenditure in obese mice. Data from people with obesity support the notion that hepatic GABA production and transport are associated with serum insulin, homeostatic model assessment for insulin resistance (HOMA-IR), T2D, and BMI. These results support a key role for hepatocyte GABA production in the dysfunctional glucoregulation and feeding behavior associated with obesity.
Topics: 4-Aminobutyrate Transaminase; Animals; Biomarkers; Diet, High-Fat; Energy Metabolism; Feeding Behavior; Glucose; Glucose Clamp Technique; Homeostasis; Humans; Hyperinsulinism; Hyperphagia; Insulin Resistance; Liver; Male; Mice, Inbred C57BL; Mice, Obese; Obesity; Vagotomy; Vagus Nerve; gamma-Aminobutyric Acid; Mice
PubMed: 34192532
DOI: 10.1016/j.celrep.2021.109301 -
Obesity Reviews : An Official Journal... Nov 2022Researchers are currently debating whether theories of addiction explain compulsive overeating of highly processed (HP) foods (i.e., industrially created foods high in... (Review)
Review
Researchers are currently debating whether theories of addiction explain compulsive overeating of highly processed (HP) foods (i.e., industrially created foods high in refined carbohydrates and/or fat), which contributes to obesity and diet-related disease. A subset of individuals consumes HP foods with behavioral phenotypes that mirror substance use disorders. Withdrawal, the emergence of aversive physical and psychological symptoms upon reduction or cessation of substance use, is a core component of addiction that was central to historical debates about other substances' addictive potential (e.g., nicotine and cocaine). However, no one has systematically considered evidence for whether HP foods cause withdrawal, which represents a key knowledge gap regarding the utility of addiction models for understanding compulsive overeating. Thus, we reviewed evidence for whether animals and humans exhibit withdrawal when reducing or eliminating HP food intake. Controlled experimental evidence indicates animals experience HP food withdrawal marked by neural reward changes and behaviors consistent with withdrawal from other addictive substances. In humans, preliminary evidence supports subjective withdrawal-like experiences. However, most current human research is limited to retrospective recall. Further experimental research is needed to evaluate this construct. We outline future research directions to investigate HP food withdrawal in humans and consider potential clinical implications.
Topics: Animals; Behavior, Addictive; Carbohydrates; Cocaine; Fast Foods; Feeding Behavior; Humans; Hyperphagia; Nicotine; Retrospective Studies; Substance-Related Disorders
PubMed: 36196649
DOI: 10.1111/obr.13507 -
Nutrients Sep 2014The idea that specific kind of foods may have an addiction potential and that some forms of overeating may represent an addicted behavior has been discussed for decades.... (Review)
Review
The idea that specific kind of foods may have an addiction potential and that some forms of overeating may represent an addicted behavior has been discussed for decades. In recent years, the interest in food addiction is growing and research on this topic lead to more precise definitions and assessment methods. For example, the Yale Food Addiction Scale has been developed for the measurement of addiction-like eating behavior based on the diagnostic criteria for substance dependence of the fourth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). In 2013, diagnostic criteria for substance abuse and-dependence were merged, thereby increasing the number of symptoms for substance use disorders (SUDs) in the DSM-5. Moreover, gambling disorder is now included along SUDs as a behavioral addiction. Although a plethora of review articles exist that discuss the applicability of the DSM-IV substance dependence criteria to eating behavior, the transferability of the newly added criteria to eating is unknown. Thus, the current article discusses if and how these new criteria may be translated to overeating. Furthermore, it is examined if the new SUD criteria will impact future research on food addiction, for example, if "diagnosing" food addiction should also be adapted by considering all of the new symptoms. Given the critical response to the revisions in DSM-5, we also discuss if the recent approach of Research Domain Criteria can be helpful in evaluating the concept of food addiction.
Topics: Behavior, Addictive; Diagnostic and Statistical Manual of Mental Disorders; Diet; Feeding Behavior; Feeding and Eating Disorders; Food; Humans; Hyperphagia; Obesity; Substance-Related Disorders
PubMed: 25230209
DOI: 10.3390/nu6093653