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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity is a global and growing problem. The detrimental health consequences of obesity are significant and include co-morbidities such as diabetes, cancer and coronary heart disease. The marked rise in obesity observed over the last three decades suggests that behavioural and environmental factors underpin the chronic mismatch between energy intake and energy expenditure. However, not all individuals become obese, suggesting that there is considerable variation in responsiveness to 'obesogenic' environments. Some individuals defend easily against a propensity to accumulate fat mass and become overweight whilst others are predisposed to gain weight, possibly as a function of genotype. The genetic contribution to obesity is well established. Common obesity is polygenic, involving complex gene-gene and gene-environment interactions, and it is these interactions that produce the multi-factorial obese phenotypes. Candidate gene variants for polygenic obesity appear to disrupt pathways involved in the regulation of energy intake and expenditure and include adrenergic receptors, uncoupling proteins, PPARG, POMC, MC4R and a set of single nucleotide polymorphisms in the FTO locus. Notably, the FTO gene is the most robust gene for common obesity characterised to date, and recent data shows that the FTO locus seems to confer risk of obesity through increasing energy intake and reduced satiety. Gene variants involved in pathways regulating addiction and reward behaviours may also play a role in predisposition to obesity. Understanding the routes through which the genotype is expressed will ultimately provide opportunities for developing strategies to intervene, as the interaction between genotype and environment is potentially modifiable through behaviour change.
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PMID:Gene-environment interactions in obesity. 1995 87

On the horizon there is a new class of psychoactive medications which work by inhibiting the neuronal reuptake of serotonin, norepinephrine, and dopamine. There are multiple potential indications for these drugs. Research suggests that they may have a role in treating depressive disorders, and it is plausible they may have potential efficacy in obesity, addiction, and pain syndromes. The current review describes some of the molecules in development presently and explores the research relevant to possible clinical uses for this class of medications.
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PMID:Triple reuptake inhibitors: a premise and promise. 2004 57

Increasing evidence underscores overlapping neurobiological pathways to addiction and obesity. In both conditions, reward processing of preferred stimuli is enhanced, whereas the executive control system that would normally regulate reward-driven responses is altered. This abnormal interaction can be greater in adolescence, a period characterized by relative immaturity of executive control systems coupled with the relative maturity of reward processing systems. The aim of this study is to explore neuropsychological performance of adolescents with excess weight (n = 27, BMI range 24-51 kg/m(2)) vs. normal-weight adolescents (n = 34, BMI range 17-24 kg/m(2)) on a comprehensive battery of executive functioning tests, including measures of working memory (letter-number sequencing), reasoning (similarities), planning (zoo map), response inhibition (five-digit test (FDT)-interference and Stroop), flexibility (FDT-switching and trail-making test (TMT)), self-regulation (revised-strategy application test (R-SAT)), and decision-making (Iowa gambling task (IGT)). We also aimed to explore personality traits of impulsivity and sensitivity to reward. Independent sample t- and Z Kolmogorov-Smirnov tests showed significant differences between groups on indexes of inhibition, flexibility, and decision-making (excess-weight participants performed poorer than controls), but not on tests of working memory, planning, and reasoning, nor on personality measures. Moreover, regression models showed a significant association between BMI and flexibility performance. These results are indicative of selective alterations of particular components of executive functions in overweight adolescents.
Obesity (Silver Spring) 2010 Aug
PMID:Selective alterations within executive functions in adolescents with excess weight. 2005 76

Dysregulation of the dopamine system is linked to various aberrant behaviors, including addiction, compulsive exercise, and hyperphagia leading to obesity. The goal of the present experiments was to determine how dopamine contributes to the expression of opposing phenotypes, excessive exercise and obesity. We hypothesized that similar alterations in dopamine and dopamine-related gene expression may underly obesity and excessive exercise, as competing traits for central reward pathways. Moreover, we hypothesized that selective breeding for high levels of exercise or obesity may have influenced genetic variation controlling these pathways, manifesting as opposing complex traits. Dopamine, dopamine-related peptide concentrations, and gene expression were evaluated in dorsal striatum (DS) and nucleus accumbens (NA) of mice from lines selectively bred for high rates of wheel running (HR) or obesity (M16), and the non-selected ICR strain from which these lines were derived. HPLC analysis showed significantly greater neurotransmitter concentrations in DS and NA of HR mice compared to M16 and ICR. Microarray analysis showed significant gene expression differences between HR and M16 compared to ICR in both brain areas, with changes revealed throughout the dopamine pathway including D1 and D2 receptors, associated G-proteins (e.g., Golf), and adenylate cyclase (e.g., Adcy5). The results suggest that similar modifications within the dopamine system may contribute to the expression of opposite phenotypes in mice, demonstrating that alterations within central reward pathways can contribute to both obesity and excessive exercise.
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PMID:Dopaminergic dysregulation in mice selectively bred for excessive exercise or obesity. 2015 88

For more than half a century, since the beginning of formal diagnostics, our psychiatric nosology has compartmentalized the compulsive pursuit of substance (e.g., alcohol, cocaine, heroin, nicotine) from nonsubstance (e.g., gambling, food, sex) rewards. Emerging brain, behavioral, and genetic findings challenge this diagnostic boundary, pointing to shared vulnerabilities underlying the pathological pursuit of substance and nonsubstance rewards. Working groups for the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V), are thus considering whether the nosologic boundaries of addiction should be redrawn to include nonsubstance disorders, such as gambling. This review discusses how neurobiological data from problem gambling, obesity, and "normal" states of attachment (romantic infatuation, sexual attraction, maternal bonds) may help us in the task of carving addictions "at a new joint." Diagnostic recarving may have a positive effect on addiction research, stimulating discovery of "crossover" pharmacotherapies with benefit for both substance and nonsubstance addictions.
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PMID:Shared brain vulnerabilities open the way for nonsubstance addictions: carving addiction at a new joint? 2020 59

Obesity and binge eating disorder are detrimental health conditions that are associated with lower qualities of life. Individuals with obesity often face societal discrimination and frequently experience related medical disorders such as diabetes, hypertension, and hyperlipidemia. Current research suggests neurobiological similarities between obesity, binge eating disorder, and substance dependence. In addition, behavioral similarities link the two conditions; obese and substance dependent individuals often report similar features such as loss of control towards food or substances, respectively, and cravings. Treatment options for obesity have begun to use this information to formulate pharmacological and therapeutic interventions that may provide greater results for weight loss and decreased binge frequency. Similarly, treatment approaches to substance addictions should consider aspects of weight management. Findings from research and treatment studies are presented with the aim of reviewing the current literature of obesity within the context of an addiction framework and providing information on empirically supported approaches to the treatment of co-occurring obesity and substance addiction.
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PMID:The Treatment of Obesity and Its Co-occurrence with Substance Use Disorders. 2022 68

We found that development of obesity was coupled with emergence of a progressively worsening deficit in neural reward responses. Similar changes in reward homeostasis induced by cocaine or heroin are considered to be crucial in triggering the transition from casual to compulsive drug-taking. Accordingly, we detected compulsive-like feeding behavior in obese but not lean rats, measured as palatable food consumption that was resistant to disruption by an aversive conditioned stimulus. Striatal dopamine D2 receptors (D2Rs) were downregulated in obese rats, as has been reported in humans addicted to drugs. Moreover, lentivirus-mediated knockdown of striatal D2Rs rapidly accelerated the development of addiction-like reward deficits and the onset of compulsive-like food seeking in rats with extended access to palatable high-fat food. These data demonstrate that overconsumption of palatable food triggers addiction-like neuroadaptive responses in brain reward circuits and drives the development of compulsive eating. Common hedonic mechanisms may therefore underlie obesity and drug addiction.
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PMID:Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. 3055 74

Because obesity is a risk factor for many serious illnesses such as diabetes, better understandings of obesity and eating disorders have been attracting attention in neurobiology, psychiatry, and neuroeconomics. This paper presents future study directions by unifying (i) economic theory of addiction and obesity [4-6], and (ii) recent empirical findings in neuroeconomics and neurobiology of obesity and addiction. It is suggested that neurobiological substrates such as adiponectin, dopamine (D2 receptors), endocannabinoids, ghrelin, leptin, nesfatin-1, norepinephrine, orexin, oxytocin, serotonin, vasopressin, CCK, GLP-1, MCH, PYY, and stress hormones (e.g., CRF) in the brain (e.g., OFC, VTA, NAcc, and the hypothalamus) may determine parameters in the economic theory of obesity. Also, the importance of introducing time-inconsistent and gain/loss-asymmetrical temporal discounting (intertemporal choice) models based on Tsallis' statistics and incorporating time-perception parameters into the neuroeconomic theory is emphasized. Future directions in the application of the theory to studies in neuroeconomics and neuropsychiatry of obesity at the molecular level, which may help medical/psychopharmacological treatments of obesity (e.g., with sibutramine), are discussed.
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PMID:Toward molecular neuroeconomics of obesity. 2046 3

Clinical and experimental observations show individual differences in the development of addiction. Increasing evidence supports the hypothesis that dopamine receptor availability in the nucleus accumbens (NAc) predisposes drug reinforcement. Here, modeling striatal-midbrain dopaminergic circuit, we propose a reinforcement learning model for addiction based on the actor-critic model of striatum. Modeling dopamine receptors in the NAc as modulators of learning rate for appetitive--but not aversive--stimuli in the critic--but not the actor--we define vulnerability to addiction as a relatively lower learning rate for the appetitive stimuli, compared to aversive stimuli, in the critic. We hypothesize that an imbalance in this learning parameter used by appetitive and aversive learning systems can result in addiction. We elucidate that the interaction between the degree of individual vulnerability and the duration of exposure to drug has two progressive consequences: deterioration of the imbalance and establishment of an abnormal habitual response in the actor. Using computational language, the proposed model describes how development of compulsive behavior can be a function of both degree of drug exposure and individual vulnerability. Moreover, the model describes how involvement of the dorsal striatum in addiction can be augmented progressively. The model also interprets other forms of addiction, such as obesity and pathological gambling, in a common mechanism with drug addiction. Finally, the model provides an answer for the question of why behavioral addictions are triggered in Parkinson's disease patients by D2 dopamine agonist treatments.
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PMID:Individual differences in nucleus accumbens dopamine receptors predict development of addiction-like behavior: a computational approach. 2056 76

Obesity has become a major health problem and epidemic. However, much of the current debate has been fractious and etiologies of obesity have been attributed to eating behavior or fast food, personality issues, depression, addiction, or genetics. One of the interesting new hypotheses for epidemic obesity is food addiction, which is associated with both substance-related disorder and eating disorder. Accumulating evidences have shown that there are many shared neural and hormonal pathways as well as distinct differences that may help researchers find why certain individuals overeat and become obese. Functional neuroimaging studies have further revealed that good or great smelling, looking, tasting, and reinforcing food has characteristics similar to that of drugs of abuse. Many of the brain changes reported for hedonic eating and obesity are also seen in various forms of addictions. Most importantly, overeating and obesity may have an acquired drive like drug addiction with respect to motivation and incentive; craving, wanting, and liking occur after early and repeated exposures to stimuli. The acquired drive for great food and relative weakness of the satiety signal would cause an imbalance between the drive and hunger/reward centers in the brain and their regulation.
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PMID:Food addiction and obesity: evidence from bench to bedside. 2064 9


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