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

Increasing rates of obesity have alarmed health officials and prompted much public dialogue. While the factors leading to obesity are numerous, an inability to control intake of freely available food is central to the problem. In order to understand this, we need to better define the mechanisms by which the brain regulates food intake, and why it is often difficult to control consumption. From this point of view, it seems valuable to consider the commonalities between food intake and drug abuse. While research in the two fields has historically emphasized different neural substrates, recent data have increased interest in better defining elements that may underlie both drug addiction and obesity. Here we discuss some of these shared elements with an emphasis on emerging areas of research that better define common mechanisms leading to overconsumption.
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PMID:Neural mechanisms underlying obesity and drug addiction. 1729 26

There is considerable evidence that the endocannabinoid (endogenous cannabinoid) system plays a significant role in appetitive drive and associated behaviours. It is therefore reasonable to hypothesize that the attenuation of the activity of this system would have therapeutic benefit in treating disorders that might have a component of excess appetitive drive or over-activity of the endocannabinoid system, such as obesity, ethanol and other drug abuse, and a variety of central nervous system and other disorders. Towards this end, antagonists of cannabinoid receptors have been designed through rational drug discovery efforts. Devoid of the abuse concerns that confound and impede the use of cannabinoid receptor agonists for legitimate medical purposes, investigation of the use of cannabinoid receptor antagonists as possible pharmacotherapeutic agents is currently being actively investigated. The compound furthest along this pathway is rimonabant, a selective CB(1) (cannabinoid receptor subtype 1) antagonist, or inverse agonist, approved in the European Union and under regulatory review in the United States for the treatment of obesity. This article summarizes the basic science of the endocannabinoid system and the therapeutic potential of cannabinoid receptor antagonists, with emphasis on the treatment of obesity.
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PMID:The endocannabinoid system and rimonabant: a new drug with a novel mechanism of action involving cannabinoid CB1 receptor antagonism--or inverse agonism--as potential obesity treatment and other therapeutic use. 1748 73

People with schizophrenia are at greater risk of obesity, Type 2 diabetes, dyslipidaemia and hypertension than the general population. This results in an increased incidence of cardiovascular disease (CVD) and reduced life expectancy, over and above that imposed by their mental illness through suicide. Several levels of evidence from data linkage analyses to clinical trials demonstrate that treatment-related metabolic disturbances are commonplace in this patient group, and that the use of certain second-generation antipsychotics may compound the risk of developing the metabolic syndrome and CVD. In addition, smoking, poor diet, reduced physical activity and alcohol or drug abuse are prevalent in people with schizophrenia and contribute to the overall CVD risk. Management and minimization of metabolic risk factors are pertinent when providing optimal care to patients with schizophrenia. This review recommends a framework for the assessment, monitoring and management of patients with schizophrenia in the UK clinical setting.
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PMID:Minimising metabolic and cardiovascular risk in schizophrenia: diabetes, obesity and dyslipidaemia. 1765 24

The endocannabinoid system (EC) plays a significant role in appetite drive and associated behaviours. Therefore attenuation of the activity of the EC system would have therapeutic benefit in treating disorders that might have a component of excess appetite drive or over-activity of the endocannabinoid system, such as obesity, ethanol and other drug abuse, and a variety of central nervous system and other disorders. Antagonists of cannabinoid receptors have been designed through rational drug discovery essential to exploit these novel targets for potential in obesity, metabolism, addiction, pain and neurologic disorders. Rimonabant is the only compound in this group which along this pathway is now approved as a selective CB (1) (cannabinoid receptor subtype 1) antagonist, or inverse agonist, in the European Union and India and under regulatory review in the United States for the treatment of obesity and associated cardiometabolic risk.
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PMID:Endocannabinoid system--a novel target for cardiometabolic risk. 1787

The increase in the incidence of obesity and eating disorders has encouraged research efforts aimed at understanding the etiology of abnormal eating behaviors. Clinical reports have led to the suggestion that some individuals may develop addictive-like behaviors when consuming palatable foods. Binge eating is a behavioral component of bulimia and obesity and has also become increasingly common in nonclinical populations in our society. This review summarizes the behavioral and neurochemical similarities between binge eating of palatable foods and the administration of drugs of abuse. An animal model of bingeing on sugar is used to illustrate behaviors found with some drugs of abuse, such as opiate-like withdrawal signs, enhanced intake following abstinence, and cross-sensitization. Related neurochemical changes commonly observed with drugs of abuse, including changes in dopamine and acetylcholine release in the nucleus accumbens, can also be found with bingeing on sugar. These neurochemical alterations are exacerbated when animals binge on sugar while at a low body weight or when the food they ingest is purged. Drawing on other animal models and the clinical literature, parallels between drug abuse and binge-eating behavior are discussed.
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PMID:Examining the addictive-like properties of binge eating using an animal model of sugar dependence. 1792 82

Chemically, TDIQ (5,6,7,8-tetrahydro-1,3-dioxolo[4,5-g]isoquinoline) can be viewed as a conformationally restricted phenylalkylamine that is related in structure to amphetamine but does not stimulate (or depress) locomotor activity in rodents. In radioligand binding studies TDIQ displays selective affinity for alpha(2)-adrenergic receptor subsites (i.e., alpha(2A)-, alpha(2B)-, and alpha(2C)-adrenergic receptors), and behavioral data suggest that it might exert an agonist (or partial agonist) effect at alpha(2)-adrenergic receptors or interact at alpha(2)-adrenergic heteroreceptors. Drug discrimination studies in rats indicate that TDIQ: (1) serves as a discriminative stimulus, (2) may be useful in the treatment of symptoms associated with the abuse of cocaine, and (3) exhibits a low potential for abuse. In addition, TDIQ exhibits a dose-dependent and wide dissociation between doses that produce an anxiolytic-like effect or an inhibition of "snack" consumption in mice and doses that produce minimal, if any, effects in tests that measure a potential for disruption of coordinated movement or motor activity. Also, TDIQ displays negligible effects on the heart rate (HR) and blood pressure (BP) of mice. Taken together, the preclinical data suggest that TDIQ exhibits a favorable ratio of therapeutic-like effects (anxiolytic, therapeutic adjunct in the treatment of cocaine abuse, and appetite suppression) to side effect-like activities (behavioral impairment, drug abuse, or adverse cardiovascular effect). As such, TDIQ could: (1) be a forerunner for a new type of chemical entity in the treatment of certain forms of anxiety and/or obesity and (2) serve as a structural template in the discovery and development of additional agents that might be selective for alpha(2)-adrenergic receptors.
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PMID:TDIQ (5,6,7,8-tetrahydro-1,3-dioxolo [4,5-g]isoquinoline): discovery, pharmacological effects, and therapeutic potential. 1807 26

The study examined the simultaneous longitudinal relationships of cigarette use in adolescence to continuing cigarette use, psychological distress, physical activity, subjective rating of health in emerging adulthood and, finally, to body mass index (BMI) in early adulthood. The study utilized data (N=414) from a drug abuse prevention trial, Midwestern Prevention Project, with subjects participating from ages 11-34 years. Structural equation modeling showed that cigarette use in early adolescence had direct paths to distress in the beginning of emerging adulthood, which in turn had significant relationships to cigarette use, physical activity, and subjective rating of health in mid-emerging adulthood. Finally, both cigarette use and physical activity had significant negative relationships to BMI in early adulthood. Results suggest that prevention programs that have been previously applied to either cigarette use or distress prevention might be re-examined for their potential to also affect obesity risk in adulthood.
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PMID:Early cigarette use and psychological distress as predictors of obesity risk in adulthood. 1823 97

Heart failure is one of the leading causes of mortality in the western world and encompasses a wide spectrum of cardiac pathologies. When the heart experiences extended periods of elevated workload, it undergoes hypertrophic enlargement in response to the increased demand. Cardiovascular disease, such as that caused by myocardial infarction, obesity or drug abuse promotes cardiac myocyte hypertrophy and subsequent heart failure. A number of signalling modulators in the vasculature milieu are known to regulate heart mass including those that influence gene expression, apoptosis, cytokine release and growth factor signalling. Recent evidence using genetic and cellular models of cardiac hypertrophy suggests that pathological hypertrophy can be prevented or reversed and has promoted an enormous drive in drug discovery research aiming to identify novel and specific regulators of hypertrophy. In this review we describe the molecular characteristics of cardiac hypertrophy such as the aberrant re-expression of the fetal gene program. We discuss the various molecular pathways responsible for the co-ordinated control of the hypertrophic program including: natriuretic peptides, the adrenergic system, adhesion and cytoskeletal proteins, IL-6 cytokine family, MEK-ERK1/2 signalling, histone acetylation, calcium-mediated modulation and the exciting recent discovery of the role of microRNAs in controlling cardiac hypertrophy. Characterisation of the signalling pathways leading to cardiac hypertrophy has led to a wealth of knowledge about this condition both physiological and pathological. The challenge will be translating this knowledge into potential pharmacological therapies for the treatment of cardiac pathologies.
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PMID:Molecular regulation of cardiac hypertrophy. 1840 81

This review covers recent progress in the discovery of selective glucocorticoid receptor (GR) antagonists. Potential therapeutic applications of selective GR antagonists are described including the pharmacological rationale and, in some cases, clinical evidence that underlies these proposed uses. Disease areas that are discussed are Cushing's syndrome, psychotic depression, diabetes, obesity, Alzheimer's disease, neuropathic pain, drug abuse, and glaucoma. Methods for evaluating GR antagonist properties (binding, functional, and in vivo assays) are briefly covered. Early research on steroidal ligands which led to the identification of the non-selective GR antagonist RU-486 (mifepristone) and the GR-selective steroid RU-43044 is reviewed as is subsequent work on related steroidal compounds. Structure activity relationships (SAR) of nonsteroidal GR antagonists from the following structural classes are presented: octahydrophenanthrenes, spirocyclic dihydropyridines, triphenylmethanes and diaryl ethers, chromenes, dibenzyl anilines, dihydroisoquinolines, pyrimidinediones, azadecalins, and aryl pyrazolo azadecalins.
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PMID:Glucocorticoid receptor antagonists. 1853 90

Drugs and food exert their reinforcing effects in part by increasing dopamine (DA) in limbic regions, which has generated interest in understanding how drug abuse/addiction relates to obesity. Here, we integrate findings from positron emission tomography imaging studies on DA's role in drug abuse/addiction and in obesity and propose a common model for these two conditions. Both in abuse/addiction and in obesity, there is an enhanced value of one type of reinforcer (drugs and food, respectively) at the expense of other reinforcers, which is a consequence of conditioned learning and resetting of reward thresholds secondary to repeated stimulation by drugs (abuse/addiction) and by large quantities of palatable food (obesity) in vulnerable individuals (i.e. genetic factors). In this model, during exposure to the reinforcer or to conditioned cues, the expected reward (processed by memory circuits) overactivates the reward and motivation circuits while inhibiting the cognitive control circuit, resulting in an inability to inhibit the drive to consume the drug or food despite attempts to do so. These neuronal circuits, which are modulated by DA, interact with one another so that disruption in one circuit can be buffered by another, which highlights the need of multiprong approaches in the treatment of addiction and obesity.
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PMID:Overlapping neuronal circuits in addiction and obesity: evidence of systems pathology. 1864 Sep 12


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