Liraglutide attenuates nicotine self-administration as well as nicotine seeking and hyperphagia during withdrawal in male and female rats.

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.

d-Allulose Inhibits Ghrelin-Responsive, Glucose-Sensitive and Neuropeptide Y Neurons in the Arcuate Nucleus and Central Injection Suppresses Appetite-Associated Food Intake in Mice.

d-allulose, a rare sugar, has sweetness with few calories. d-allulose regulates feeding and glycemia, and ameliorates hyperphagia, obesity and diabetes. All these functions involve the central nervous system. However, central mechanisms underlying these effects of d-allulose remain unknown. We recently reported that d-allulose activates the anorexigenic neurons in the hypothalamic arcuate nucleus (ARC), the neurons that respond to glucagon-like peptide-1 and that express proopiomelanocortin. However, its action on the orexigenic neurons remains unknown. This study investigated the effects of d-allulose on the ARC neurons implicated in hunger, by measuring cytosolic Ca2+ concentration ([Ca2+]i) in single neurons. d-allulose depressed the increases in [Ca2+]i induced by ghrelin and by low glucose in ARC neurons and inhibited spontaneous oscillatory [Ca2+]i increases in neuropeptide Y (NPY) neurons. d-allulose inhibited 10 of 35 (28%) ghrelin-responsive, 18 of 60 (30%) glucose-sensitive and 3 of 8 (37.5%) NPY neurons in ARC. Intracerebroventricular injection of d-allulose inhibited food intake at 20:00 and 22:00, the early dark phase when hunger is promoted. These results indicate that d-allulose suppresses hunger-associated feeding and inhibits hunger-promoting neurons in ARC. These central actions of d-allulose represent the potential of d-allulose to inhibit the hyperphagia with excessive appetite, thereby counteracting obesity and diabetes.

Prader-Willi Syndrome: Possibilities of Weight Gain Prevention and Treatment.

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.

Pediatric weight management interventions improve prevalence of overeating behaviors.

OBJECTIVE: To examine changes in prevalence of overeating behaviors in a comparative effectiveness study of two pediatric weight management interventions. METHODS: Four-hundred and seven children, ages 6-12 years, with a BMI ≥ 85th percentile were enrolled in a comparative effectiveness trial of two pediatric weight management interventions. Prevalence of "sneaking, hiding or hoarding food", and 'eating in the absence of hunger' was evaluated at baseline and 12 months. Statistical methods included McNemar's test and longitudinal logistic regression. RESULTS: Prevalence of "sneak, hide, or hoard food" significantly decreased in all participants from 29.1% to 20.7% at 12 months. The prevalence of "eating in the absence of hunger" decreased in all participants from 46.7% to 22.4% at 12 months. Use of SNAP benefits, free/reduced meals at school, parental stress, housing, and food insecurity at baseline were associated with an increased likelihood of endorsing overeating behaviors at 12 months. Conversely, those who engaged in at least one session of the pediatric weight management intervention were significantly less likely to endorse "eating in the absence of hunger" at 12 months. CONCLUSIONS: Participation in pediatric weight management interventions improves the prevalence of overeating behaviors and is associated with participant engagement and social determinants of health, specifically food security status. Efforts to engage populations impacted by food insecurity and other social determinants of health risk factors will be critical for success of weight management interventions. CLINICAL TRIAL REGISTRATION: This trial has been registered at ClinicalTrials.gov (identifier: NCT03012126).

Assessment of chronic disease self-management in patients with chronic heart failure based on the MCID of patient-reported outcomes by the multilevel model.

PURPOSE: The minimal clinically important difference (MCID) of a patient-reported outcome (PRO) represents the threshold value of the change in the score for that PRO. It is deemed to have an important implication in clinical management. This study was performed to evaluate the clinical significance of chronic disease self-management (CDSM) for patients with chronic heart failure based on the MCID of the chronic heart failure-PRO measure (CHF-PROM). METHODS: A multicenter, prospective cohort study of 555 patients with heart failure were enrolled from July 2018. Advice of CDSM was provided in written form at discharge to all patients. Information regarding CHF-PROM and CDSM were collected during follow-up. Multilevel models were applied to dynamically evaluate the effects of CDSM for CHF-PROM scores, as well as its physical and psychological domains. MCID changes of the PRO were introduced and compared with ß values of CDSM obtained from the multi-level models to further evaluate the clinical significance. The STROBE checklist is shown in Additional file 1. RESULTS: Scores for CHF-PROM improved significantly after discharge. The multilevel models showed that a regular schedule, avoidance of over-eating, a low-sodium diet and exercise increased scores on CHF-PROM. Compared with the MCID, avoidance of over-eating (12.39 vs. 9.75) and maintenance of a regular schedule often (10.98 vs. 9.75), and exercise almost every day (11.36 vs. 9.75) reached clinical significance for the overall summary. Avoidance of over-eating (5.88 vs. 4.79) and a regular schedule almost every day (4.96 vs. 4.79) reached clinical significance for the physical scores. Avoidance of over-eating half of the time (5.26 vs. 4.87) and a regular schedule almost every day (5.84 vs. 4.87) demonstrated clinical significance for the psychological scores. CONCLUSIONS: This study observed an association of avoidance of over-eating and maintenance of a regular schedule with the improvement of CHF-PROM. It provides further evidence for management of heart failure. TRIAL REGISTRATION: Current Prospective Trials NCT02878811; registered August 25, 2016; https://clinicaltrials.gov/ct2/show/NCT02878811?term=NCT02878811&draw=2&rank=1 .

Inhibition of mitochondrial fission and iNOS in the dorsal vagal complex protects from overeating and weight gain.

OBJECTIVES: The dorsal vagal complex (DVC) senses insulin and controls glucose homeostasis, feeding behaviour and body weight. Three-days of high-fat diet (HFD) in rats are sufficient to induce insulin resistance in the DVC and impair its ability to regulate feeding behaviour. HFD-feeding is associated with increased dynamin-related protein 1 (Drp1)-dependent mitochondrial fission in the DVC. We investigated the effects that altered Drp1 activity in the DVC has on feeding behaviour. Additionally, we aimed to uncover the molecular events and the neuronal cell populations associated with DVC insulin sensing and resistance. METHODS: Eight-week-old male Sprague Dawley rats received DVC stereotactic surgery for brain infusion to facilitate the localised administration of insulin or viruses to express mutated forms of Drp1 or to knockdown inducible nitric oxide synthase (iNOS) in the NTS of the DVC. High-Fat diet feeding was used to cause insulin resistance and obesity. RESULTS: We showed that Drp1 activation in the DVC increases weight gain in rats and Drp1 inhibition in HFD-fed rats reduced food intake, weight gain and adipose tissue. Rats expressing active Drp1 in the DVC had higher levels of iNOS and knockdown of DVC iNOS in HFD-fed rats led to a reduction of food intake, weight gain and adipose tissue. Finally, inhibiting mitochondrial fission in DVC astrocytes was sufficient to protect rats from HFD-dependent insulin resistance, hyperphagia, weight gain and fat deposition. CONCLUSION: We uncovered new molecular and cellular targets for brain regulation of whole-body metabolism, which could inform new strategies to combat obesity and diabetes.

Current and emerging therapies for managing hyperphagia and obesity in Prader-Willi syndrome: A narrative review.

In early childhood, individuals with Prader-Willi syndrome (PWS) experience excess weight gain and severe hyperphagia with food compulsivity, which often leads to early onset morbid obesity. Effective treatments for appetite suppression and weight control are currently unavailable for PWS. Our aim to further understand the pathogenesis of PWS led us to carry out a comprehensive search of the current and emerging therapies for managing hyperphagia and extreme weight gain in PWS. A literature search was performed using PubMed and the following keywords: "PWS" AND "therapy" OR "[drug name]"; reference lists, pharmaceutical websites, and the ClinicalTrials.gov registry were also reviewed. Articles presenting data from current standard treatments in PWS and also clinical trials of pharmacological agents in the pipeline were selected. Current standard treatments include dietary restriction/modifications, exercise, and growth hormone replacement, which appear to have limited efficacy for appetite and weight control in patients with PWS. The long-term safety and effectiveness of bariatric surgery in PWS remains unknown. However, many promising pharmacotherapies are in development and, if approved, will bring much needed choices into the PWS pharmacological armamentarium. With the progress that is currently being made in our understanding of PWS, an effective treatment may not be far off.

Blunted leptin sensitivity during hedonic overeating can be reinstated by activating galanin 2 receptors (Gal2R) in the lateral hypothalamus.

AIM: Since foods with high hedonic value are often consumed in excess of energetic needs, this study was designed to identify the mechanisms that may counter anorexigenic signalling in the presence of hedonic foods in lean animals. METHODS: Mice, in different states of satiety (fed/fasted, or fed/fasted and treated with ghrelin or leptin, respectively), were allowed to choose between high-fat/high-sucrose and standard foods. Intake of each food type and the activity of hypothalamic neuropetidergic neurons that regulate appetite were monitored. In some cases, food choice was monitored in leptin-injected fasted mice that received microinjections of galanin receptor agonists into the lateral hypothalamus. RESULTS: Appetite-stimulating orexin neurons in the lateral hypothalamus are rapidly activated when lean, satiated mice consume a highly palatable food (PF); such activation (upregulated c-Fos expression) occurred even after administration of the anorexigenic hormone leptin and despite intact leptin signalling in the hypothalamus. The ability of leptin to restrain PF eating is restored when a galanin receptor 2 (Gal2R) agonist is injected into the lateral hypothalamus. CONCLUSION: Hedonically-loaded foods interrupt the inhibitory actions of leptin on orexin neurons and interfere with the homeostatic control of feeding. Overeating of palatable foods can be curtailed in lean animals by activating Gal2R in the lateral hypothalamus.

Vitamin C protects against chronic social isolation stress-induced weight gain and depressive-like behavior in adult male rats.

Objective. Considering the importance of ghrelin in stress-induced hyperphagia and a role of antioxidants in decreasing body weight, in the present study, the effect of vitamin C (VitC) on ghrelin secretion and food intake following chronic social isolation (CIS) was evaluated in rats.Methods. Thirty two male Wistar rats (200-220g) were randomly divided into: control, VitC, CIS, and CIS + VitC groups. Animals received VitC (500 mg/kg/day)/saline by gavage for 3 weeks. For 24 h cumulative and post 18-20 h fasting food intake, fasting plasma ghrelin level, and body weight were measured. Gastric histopathology was also evaluated.Results. Results showed a marked increase in fasting plasma ghrelin and food intake in stressed rats compared to controls. VitC prevented the increases in stressed rats. Histological assessment indicated a positive effect of VitC on gastric glandular cells compared to control, an effect that might partially be a reason of significant increase of plasma ghrelin levels in VitC rats. Elevated plasma ghrelin in VitC group was even higher than that one in stressed group, whereas there were no significant changes in the food intake. Assessment of the percentage of changes in body weight during 21 days showed a significant increase in stressed rats compared to controls. Vitamin C treatment prevented this increase. Stressed rats also displayed depression-like behavior as indicated by sucrose test, whereas VitC ameliorated it.Conclusions. The data of the present study indicate that VitC may overcome ghrelin-induced hyperphagia and improve the abnormal feeding and depressive behavior in CIS rats.

How best to reduce unhealthy risk-taking behaviours? A meta-review of evidence syntheses of interventions using self-regulation principles.

Self-regulation is a key antecedent of health and behaviour-change interventions have utilised self-regulation approaches to promote health. The present study used a novel methodology, a nested meta-review, to: (a) integrate and summarise information from evidence syntheses of diverse self-regulation interventions to reduce risk-taking, in the behavioural domains of smoking, alcohol and drug use, unhealthy eating, externalising problem behaviours, and sexual risk-taking; (b) identify intervention features implicated in risk-taking prevention or reduction; and (c) provide recommendations for future research and practice. Searches of eight databases yielded 21 eligible evidence syntheses, 15 taking a primarily social-cognitive strategy (k = 1,103 total studies), and 6 taking a primary trait/developmental strategy (k = 119); total N > 650,000. Intervention features most frequently associated with reduced risk-taking included: delivery of multiple components through (either, or a mix of) group, individual, computer, and one-one-one delivery; screening and pharmacotherapy, where relevant; targeting only one behavioural outcome; provision of counselling, stress-management, skills-training, self-monitoring, self-control and impulsivity training, and personalised feedback; identification of barriers and 'resolution' of barriers; tailoring to age and ethnicity; and, also, incorporating social support by peers. Some of these patterns were more visible in meta-analyses with higher methodological quality. Recommendations for research and practice are offered.

Potato-Resistant Starch Supplementation Improves Microbiota Dysbiosis, Inflammation, and Gut-Brain Signaling in High Fat-Fed Rats.

(1) High-fat (HF) diet leads to gut microbiota dysbiosis which is associated with systemic inflammation. Bacterial-driven inflammation is sufficient to alter vagally mediated satiety and induce hyperphagia. Promoting bacterial fermentation improves gastrointestinal (GI) epithelial barrier function and reduces inflammation. Resistant starch escape digestion and can be fermented by bacteria in the distal gut. Therefore, we hypothesized that potato RS supplementation in HF-fed rats would lead to compositional changes in microbiota composition associated with improved inflammatory status and vagal signaling. (2) Male Wistar rats (n = 8/group) were fed a low-fat chow (LF, 13% fat), HF (45% fat), or an isocaloric HF supplemented with 12% potato RS (HFRS) diet. (3) The HFRS-fed rats consumed significantly less energy than HF animals throughout the experiment. Systemic inflammation and glucose homeostasis were improved in the HFRS compared to HF rats. Cholecystokinin-induced satiety was abolished in HF-fed rats and restored in HFRS rats. HF feeding led to a significant decrease in positive c fiber staining in the brainstem which was averted by RS supplementation. (4) The RS supplementation prevented dysbiosis and systemic inflammation. Additionally, microbiota manipulation via dietary potato RS prevented HF-diet-induced reorganization of vagal afferent fibers, loss in CCK-induced satiety, and hyperphagia.

Uncontrolled Eating during Pregnancy Predicts Fetal Growth: The Healthy Mom Zone Trial.

Excess maternal weight gain during pregnancy elevates infants' risk for macrosomia and early-onset obesity. Eating behavior is also related to weight gain, but the relationship to fetal growth is unclear. We examined whether Healthy Mom Zone, an individually tailored, adaptive gestational weight gain intervention, and maternal eating behaviors affected fetal growth in pregnant women (n = 27) with a BMI > 24. At study enrollment (6-13 weeks gestation) and monthly thereafter, the Three-Factor Eating Questionnaire was completed. Ultrasounds were obtained monthly from 14-34 weeks gestation. Data were analyzed using multilevel modeling. Higher baseline levels of uncontrolled eating predicted faster rates of fetal growth in late gestation. Cognitive restraint was not associated with fetal growth, but moderated the effect of uncontrolled eating on fetal growth. Emotional eating was not associated with fetal growth. Among women with higher baseline levels of uncontrolled eating, fetuses of women in the control group grew faster and were larger in later gestation than those in the intervention group (study group × baseline uncontrolled eating × gestational week interaction, p = 0.03). This is one of the first intervention studies to use an individually tailored, adaptive design to manage weight gain in pregnancy to demonstrate potential effects on fetal growth. Results also suggest that it may be important to develop intervention content and strategies specific to pregnant women with high vs. low levels of disinhibited eating.

Single injection of rapamycin blocks post-food restriction hyperphagia and body-weight regain in rats.

Given the increasing prevalence of and severity of complications associated with obesity, there is great need for treatments resulting in prolonged weight loss. Long-term maintenance of weight loss requires sustained changes in food-intake and energy-expenditure strategies, which are unfortunately often taxing, resulting in a return to predieting weight. Therefore, drug therapies may facilitate greater adherence to a restricted diet and prolong weight loss. One such drug is rapamycin (RAP), a mechanistic target of rapamycin (mTOR) inhibitor. Here, we show that a single injection of RAP dampens the hyperphagic response in calorically restricted rats when they are returned to free feed immediately or 10 days after injection. Moreover, we demonstrate that a single injection of RAP given to calorically restricted rats prevents body-weight regain when animals are returned to free feed either immediately or 10 days after injection. Furthermore, we extend our previous findings that RAP does not produce malaise or illness and show that RAP does not produce any behavioral deficits that may inhibit an animal from eating. Thus, we suggest that mTOR may be a useful target in obesity research, given that its inhibition may decrease the hyperphagic response following caloric restriction. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Identificación y consecuencias de la edorexia / Identification and consequences of binge eating disorder

Introducción: Mediante la comprensión de los procesos biopsicosociales que subyacen a la ingesta excesiva de alimentos, se desea encontrar la solución a la epidemia de la obesidad. La edorexia constituye un síndrome psicológico en el que las personas que lo presentan tienen un apetito desproporcionado y excesivo. El diagnóstico diferencial de la edorexia se debe hacer con algunos de los trastornos de la conducta alimentaria y la hiperfagia inducida por fármacos. Objetivo: Realizar una breve revisión sobre la edorexia, sus aspectos conceptuales, algunas dimensiones con las que se relaciona, y su repercusión en la salud del ser humano. Método: Se utilizó como buscador de información científica Google Académico. Se emplearon como palabras clave: edorexia, trastornos de la conducta alimentaria, obesidad. Fueron evaluados artículos de revisión e investigación que, en general, tenían menos de 10 años de publicados. La búsqueda se realizó en idioma español, portugués e inglés. Los artículos seleccionados están indexados en diferentes bases de datos (PubMed, LILACS, Cochrane y SciElo), así como páginas web. Fueron excluidos aquellos que no cumplieron con los objetivos y criterios enunciados, lo que permitió el estudio de 60 documentos, de los cuales, 33 fueron referenciados. Conclusiones: Edorexia, o comer por apetito, enfatiza las conductas problemas asociadas a la obesidad, y se compone de 4 elementos fundamentales: la dependencia, la evitación, el componente emocional y el déficit de bienestar psicológico. Es causa de frecuentes secuelas físicas y psicológicas. Se debe prevenir e identificar precozmente, para realizar su adecuado tratamiento y así evitar la afectación de la calidad de vida del paciente(AU)

Introduction: A solution to the obesity epidemic is intended to be found by understanding the biopsychosocial processes underlying excessive food intake. Binge eating disorder (BED) is a psychological syndrome in which sufferers have excessive, disproportionate appetite. A differential diagnosis should be made between binge eating disorder and other eating disorders as well as drug-induced hyperphagia. Objective: Conduct a brief review about binge eating disorder, its conceptual aspects, some dimensions with which it relates, and its impact on human health. Method: Scientific information was obtained from the search engine Google Scholar using the key words binge eating disorder, eating disorders and obesity. Most of the reviews and research studies evaluated had been published in the past 10 years. The search was conducted in Spanish, Portuguese and English. The papers selected were indexed on various databases (PubMed, LILACS, Cochrane, SciELO) and webpages. After excluding papers not meeting the stated aims and criteria, the sample was composed of 60 documents of which 33 were referenced. Conclusions: Binge eating disorder, aka compulsive overeating, enhances the problem behavior associated to obesity, and consists of 4 main elements: dependence, avoidance, the emotional component and psychological well-being deficit. On the other hand, it is the cause of frequent physical and psychological disorders. Early prevention and identification as well as indication of the appropriate treatment are all fundamental so that the quality of life of patients is not affected(AU)

Identificación y consecuencias de la edorexia / Identification and consequences of binge eating disorder

Introducción: Mediante la comprensión de los procesos biopsicosociales que subyacen a la ingesta excesiva de alimentos, se desea encontrar la solución a la epidemia de la obesidad. La edorexia constituye un síndrome psicológico en el que las personas que lo presentan tienen un apetito desproporcionado y excesivo. El diagnóstico diferencial de la edorexia se debe hacer con algunos de los trastornos de la conducta alimentaria y la hiperfagia inducida por fármacos. Objetivo: Realizar una breve revisión sobre la edorexia, sus aspectos conceptuales, algunas dimensiones con las que se relaciona, y su repercusión en la salud del ser humano. Método: Se utilizó como buscador de información científica Google Académico. Se emplearon como palabras clave: edorexia, trastornos de la conducta alimentaria, obesidad. Fueron evaluados artículos de revisión e investigación que, en general, tenían menos de 10 años de publicados. La búsqueda se realizó en idioma español, portugués e inglés. Los artículos seleccionados están indexados en diferentes bases de datos (PubMed, LILACS, Cochrane y SciElo), así como páginas web. Fueron excluidos aquellos que no cumplieron con los objetivos y criterios enunciados, lo que permitió el estudio de 60 documentos, de los cuales, 33 fueron referenciados. Conclusiones: Edorexia, o comer por apetito, enfatiza las conductas problemas asociadas a la obesidad, y se compone de 4 elementos fundamentales: la dependencia, la evitación, el componente emocional y el déficit de bienestar psicológico. Es causa de frecuentes secuelas físicas y psicológicas. Se debe prevenir e identificar precozmente, para realizar su adecuado tratamiento y así evitar la afectación de la calidad de vida del paciente(AU)

Introduction: A solution to the obesity epidemic is intended to be found by understanding the biopsychosocial processes underlying excessive food intake. Binge eating disorder (BED) is a psychological syndrome in which sufferers have excessive, disproportionate appetite. A differential diagnosis should be made between binge eating disorder and other eating disorders as well as drug-induced hyperphagia. Objective: Conduct a brief review about binge eating disorder, its conceptual aspects, some dimensions with which it relates, and its impact on human health. Method: Scientific information was obtained from the search engine Google Scholar using the key words binge eating disorder, eating disorders and obesity. Most of the reviews and research studies evaluated had been published in the past 10 years. The search was conducted in Spanish, Portuguese and English. The papers selected were indexed on various databases (PubMed, LILACS, Cochrane, SciELO) and webpages. After excluding papers not meeting the stated aims and criteria, the sample was composed of 60 documents of which 33 were referenced. Conclusions: Binge eating disorder, aka compulsive overeating, enhances the problem behavior associated to obesity, and consists of 4 main elements: dependence, avoidance, the emotional component and psychological well-being deficit. On the other hand, it is the cause of frequent physical and psychological disorders. Early prevention and identification as well as indication of the appropriate treatment are all fundamental so that the quality of life of patients is not affected(AU)

Combating Excessive Eating: A Role for Four Evidence-Based Remedies.

OBJECTIVE: The aim of this study is to review the control of energy balance and outline some causes of and remedies for excessive energy intake. METHODS: A narrative review was conducted. RESULTS: There is negative feedback control of energy intake and body weight, but, nonetheless, energy intake is only loosely coupled with energy expenditure. Consequently, we are vulnerable to eating in excess of energy requirements. In this context, energy density, portion size, and habitual meal patterns have strong influences on energy intake and, accordingly, can be targeted to reduce energy intake. For example, energy density can be reduced without much affecting food reward (approximately the pleasure gained from eating) because their relationship is such that reward value is affected relatively little by increments in energy density above 1.5 kcal/g. This and other strategies that increase reward per calorie eaten may be superior to increasing the satiety effect of products because fullness is not inherently rewarding. Low-calorie sweeteners provide a means to reduce energy density while largely preserving food or beverage reward value. Consistent with this, consumption of low-calorie sweeteners compared with consumption of sugars has been found to reduce energy intake and body weight. CONCLUSIONS: Understanding what causes excessive eating also provides insights into how to combat this problem.

Exogenous nicotinamide adenine dinucleotide regulates energy metabolism via hypothalamic connexin 43.

BACKGROUND: Nicotinamide adenine dinucleotide (NAD)-dependent deacetylase SIRT1 is an important regulator of hypothalamic neuronal function. Thus, an adequate hypothalamic NAD content is critical for maintaining normal energy homeostasis. METHODS: We investigated whether NAD supplementation increases hypothalamic NAD levels and affects energy metabolism in mice. Furthermore, we investigated the mechanisms underlying the effects of exogenous NAD on central metabolism upon entering the hypothalamus. RESULTS: Central and peripheral NAD administration suppressed fasting-induced hyperphagia and weight gain in mice. Extracellular NAD was imported into N1 hypothalamic neuronal cells in a connexin 43-dependent and CD73-independent manner. Consistent with the in vitro data, inhibition of hypothalamic connexin 43 blocked hypothalamic NAD uptake and NAD-induced anorexia. Exogenous NAD suppressed NPY and AgRP transcriptional activity, which was mediated by SIRT1 and FOXO1. CONCLUSIONS: Exogenous NAD is effectively transported to the hypothalamus via a connexin 43-dependent mechanism and increases hypothalamic NAD content. Therefore, NAD supplementation is a potential therapeutic method for metabolic disorders characterized by hypothalamic NAD depletion.

Antidiabetic Activity of Afobazole in Wistar Rats.

Using the streptozotocin model of type 2 diabetes mellitus in Wistar rats, we compared antidiabetic activity of anxiolytic Afobazole with that of metformin. Afobazole in a dose of 10 mg/kg reduced streptozotocin-induced hyperglycemia and polyphagia and prevented accumulation of malonic dialdehyde, being not inferior to metformin in a dose of 300 mg/kg, and was even more effective than metformin in body weight recovery, elimination of polydipsia, and preservation of these effects after treatment withdrawal.

Metabolic and cognitive improvement from switching to saccharin or water following chronic consumption by female rats of 10% sucrose solution.

High consumption of sugar-sweetened beverages (SSBs) is a risk factor for weight gain and metabolic disease. Whether this risk is reduced by switching to 'diet' beverages containing low-calorie sweeteners (LCS) is controversial. Two experiments modeled whether a switch from SSB to LCS beverages produced positive outcomes on behavioral and metabolic measures. Both experiments consisted of a Stage 1, in which adult female rats received unrestricted access to 10% sucrose solution in addition to chow and water for 4 (Experiment 1) or 8 weeks (Experiment 2). In Stage 2 rats were switched to either saccharin (Suc-Sacch) or water (Suc-Water) or remained on 10% sucrose (Suc-Suc) for a further 4 (Experiment 1) or 7 weeks (Experiment 2). Experiment 2 contained a fourth group that was maintained on water throughout (Water-Water). In both experiments energy intake and weight gain in Stage 2 was reduced for Suc-Sacch and Suc-Water groups relative to the Suc-Suc groups and at cull the Suc-Suc groups showed poorer insulin sensitivity and greater g/kg fat than Suc-Water and Suc-Sacch groups. In Experiment 2 short-term place recognition memory was impaired at the end of Stage 1 but recovered to a similar extent in the Suc-Water and Suc-Sacch groups; when the latter groups were compared with the Water-Water group, recovery was found to be essentially complete. A higher saccharin concentration in Experiment 2 than in Experiment 1 increased absolute amounts of saccharin ingested but intake solution volumes remained low. These results show that switching from sucrose to either water or saccharin produces equivalent improvements on both metabolic and cognitive measures.

Reducing behavioural risk factors for cancer: An affect regulation perspective.

Nearly half of all cancer deaths are attributable to preventable causes, primarily unhealthy behaviours such as tobacco use, alcohol use and overeating. In this review, we argue that people engage in these behaviours, at least in part, as a means of regulating their affective states. To better understand why people engage in these behaviours and how researchers might design interventions to promote the selection of healthier methods for regulating affect, we propose a conceptual model of affect regulation. We synthesise research from both the stress and coping tradition as well as the emotion and emotion regulation tradition, two literatures that are not typically integrated. In so doing, we indicate where researchers have made headway in understanding these behaviours as affect regulation and note how our model could be used to structure future work in a way that would be particularly advantageous to cancer control efforts.