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

On 5 and 6 April 1991, at the National Research Council (CNR) in Rome, a Consensus Conference on the relationship between overweight, obesity and health was held. The conference was sponsored by FATMA (Applied Project on Disease Factors of the CNR) and UICO (Italian Society for the Study of Obesity) with the purpose of establishing guidelines for health employees. The development of the conference followed the methodology set down by OMAR to obtain a rational and significant consensus on the answers to six basic questions prepared by the planning committee. The questions were the pivotal point of the conference and were brought to the attention of all the attendees and widely diffused among the medical community; they were proposed with the aim of giving an exhaustive definition of obesity, to investigate its relationship with mortality and morbidity, to highlight its social characterization, to indicate methods of evaluation and recommendations for weight loss, to select groups at risk, and to focus general guidelines for research. After the presentation of the state of the art on 18 topics by experts in the field, the 22 members of the consensus panel, impartial experts from a vast area of the scientific community, discussed a draft document representing the answers to the questions, which was subsequently submitted to the 307 attendees, discussed and then approved. This paper is the definitive document of the Consensus Conference. The introduction explains the reasons which led to the decision to promote the conference six years after the one held in the United States. The methodology is then set out. The questions are answered in the form of recommendations and backed up by data and scientific evidence from the literature.
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PMID:Italian Consensus Conference--overweight, obesity and health. 177 63

On April 5th and 6th 1991, at the National Research Council (CNR) in Rome, a Consensus Conference on the relationship between Overweight, Obesity and Health was held. The Conference was sponsored by FATMA (Applied Project on Disease Factors of the CNR) and UICO (Italian Society for the Study of Obesity) with the purpose of establishing guidelines for health employees. The development of the Conference followed the methodology set down by OMAR to obtain a rational and significant consensus on the answers to 6 basic questions prepared by the Planning Committee. The questions were the pivotal point of the Conference and were brought to the attention of all the attendees and widely diffused among the medical community; they were proposed with the aim of giving an exhaustive definition of obesity, to investigate its relationship with mortality and morbidity, to highlight its social characterization, to indicate methods of evaluation and recommendations for weight loss, to select groups at risk, and to focus general guidelines for research. After the presentation of the state of the art on 18 topics by experts in the field, the 22 members of the Consensus Panel, impartial experts from a vast area of the scientific community, discussed a draft document representing the answers to the questions, which was subsequently illustrated to the 307 attendees, discussed and then approved. This paper is the definitive document of the Consensus Conference. The introduction explains the reasons which led to the decision to promote the Conference six years after the one held in the United States. The methodology is then set out. The questions are answered in the form of recommendations and backed up by data and scientific demonstrations from the literature.
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PMID:[Italian Consensus Conference; overweight, obesity and health (ICC S.O.S. 1991)]. 194 8

Leptin is the primary signal through which the hypothalamus senses nutritional state and modulates food intake and energy balance. Leptin reduces food intake by upregulating anorexigenic (appetite-reducing) neuropeptides, such as alpha-melanocyte-stimulating hormone, and downregulating orexigenic (appetite-stimulating) factors, primarily neuropeptide Y. Genetic defects in anorexigenic signalling, such as mutations in the melanocortin-4 (ref. 5) or leptin receptors, cause obesity. However, alternative orexigenic pathways maintain food intake in mice deficient in neuropeptide Y. CB1 cannabinoid receptors and the endocannabinoids anandamide and 2-arachidonoyl glycerol are present in the hypothalamus, and marijuana and anandamide stimulate food intake. Here we show that following temporary food restriction, CB1 receptor knockout mice eat less than their wild-type littermates, and the CB1 antagonist SR141716A reduces food intake in wild-type but not knockout mice. Furthermore, defective leptin signalling is associated with elevated hypothalamic, but not cerebellar, levels of endocannabinoids in obese db/db and ob/ob mice and Zucker rats. Acute leptin treatment of normal rats and ob/ob mice reduces anandamide and 2-arachidonoyl glycerol in the hypothalamus. These findings indicate that endocannabinoids in the hypothalamus may tonically activate CB1 receptors to maintain food intake and form part of the neural circuitry regulated by leptin.
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PMID:Leptin-regulated endocannabinoids are involved in maintaining food intake. 1129 28

Because the CB1 receptor antagonist SR141716 was previously reported to modulate food intake in rodents, we studied its efficacy in reducing obesity in a diet-induced obesity (DIO) model widely used for research on the human obesity syndrome. During a 5-wk treatment, SR141716 (10 mg. kg(-1). day(-1) orally) induced a transient reduction of food intake (-48% on week 1) and a marked but sustained reduction of body weight (-20%) and adiposity (-50%) of DIO mice. Furthermore, SR141716 corrected the insulin resistance and lowered plasma leptin, insulin, and free fatty acid levels. Most of these effects were present, but less pronounced at 3 mg. kg(-1). day(-1). In addition to its hypophagic action, SR141716 may influence metabolic processes as the body weight loss of SR141716-treated mice was significantly higher during 24-h fasting compared with vehicle-treated animals, and when a 3-day treatment was compared with a pair feeding. SR141716 had no effect in CB1 receptor knockout mice, which confirmed the implication of CB1 receptors in the activity of the compound. These findings suggest that SR141716 has a potential as a novel anti-obesity treatment.
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PMID:Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice. 1252 83

Cannabinoid CB1 receptor (CB1R) inverse agonists reduce appetite and body weight (BW) gain in various species. Exercise is thought to be a natural reward process and the cannabinoid system is also believed to influence reward. We tested the hypothesis that voluntary exercise would augment the effects of AM251, a CB1R inverse agonist, on food intake (FI) and BW loss in murine genetic models of obesity. ob/ob, agouti yellow (A(y)), and lean C57BL/6J mice were treated via oral gavage with vehicle or AM251 (1, 3, or 10 mg/kg) 1 h before the dark cycle. The suppressive effects of 3 and 10 mg/kg AM251 on overnight FI, BW gain, and water intake (WI) were significant in ob/ob mice. In contrast, in A(y) mice, 10 mg/kg AM251 decreased FI and BW gain while it did not influence WI. Food consumption of ob/ob and A(y) mice, as evidenced by feeding frequency (FF) and feeding duration (FD), was reduced by AM251 for 4-6 h. AM251 at these doses had no impact on the appetitive behavior or BW gain of lean mice. After a 1-week wash-out period, mice were given running wheels in their home cages. With running wheel exercise, lean and obese mice exhibited increased sensitivity to AM251. Low voluntary wheel running activity of ob/ob mice precluded detection of combined effects of AM251 and exercise in this genetic model of obesity. Lean and agouti mice given AM251 combined with exercise lost a greater amount of BW than with AM251 alone. Our data suggest that voluntary exercise can enhance CB1R inverse agonist effects on appetite and BW loss in both lean and agouti obese mice.
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PMID:Voluntary exercise augments acute effects of CB1-receptor inverse agonist on body weight loss in obese and lean mice. 1472 49

Gastrointestinal tract (GIT) and nervous system, both central (CNS) and enteric (ENS), are involved in two-way extrinsic communication by parasympathetic and sympathetic nerves, each comprising efferents fibers such as cholinergic and noradrenergic, respectively, and afferent sensory fibers required for gut-brain signaling. Afferent nerves are equipped with numerous sensors at their terminals in the gut related to visceral mechano- chemo- and noci-receptors, whose excitations may trigger a variety of visceral reflexes regulating GIT functions, including the appetitive behaviour. Food intake depends upon various influences from the CNS as well as from the body energy stores (adipocytes) that express and release the product of Ob gene, leptin, in proportion to fat stored and acting in long-term regulation of food intake. Leptin acts through receptors (Ob-R) present in afferent visceral nerves and hypothalamic arcuate nucleus (ARC), whose neurons are capable of expressing and releasing neuropeptide Y (NPY) and agouti related protein (AgRP) that activate the ingestive behaviour through paraventricular nucleus (PVN) (iVfeeding centerli). In addition, to this long-term regulation, a short-term regulation, on meal-to-meal basis, is secured by several gut hormones, such as cholecystokinin (CCK), peptides YY (PYY) and oxyntomodulin (OXM), released from the endocrine intestinal cells and acting via G-protein coupled receptors (GPCR) either on afferent nerves or directly on ARC neurons, which in turn inhibit expression and release of food-intake stimulating NPY and AgRP, thereby inducing satiety through inhibition of PVN. In contrast, during fasting, the GIT, especially oxyntic mucosa, expresses and releases appetite stimulating (orexigenic) factors such as ghrelin and orexins (OX) -A and OX-B, and cannabinoid CB1 agonist. Ghrelin activates growth-hormone secretagogue receptor (GHS-R) in hypothalamic ARC and stimulates growth hormone (GH) release and in vagal afferents to promote the expression and release of hypothalamic NPY and AgRP stimulating PVN and driving ingestive behaviour. The balance and interaction between anorexigenic (CCK, PYY, OXM) and orexigenic (ghrelin and OX) factors originating from GIT appears to play an important role in short-term regulation of food intake and growth hormone (GH) release. An impairment of this balance may result in disorders of feeding behaviour and weight gain (obesity) or weight loss (cachexia).
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PMID:Brain-gut axis and its role in the control of food intake. 1508 74

Acylethanolamides are endogenous compounds with lipid structure including anandamide (AEA), palmitoilethanolamide, oleylamide and oleylethanolamide (OEA). AEA binds to the cannabinoid receptor CB1, located at the central nervous system, while OEA is an endogenous ligand for the alpha subtype of peroxisome-proliferator activating receptor (PPARalpha). Since AEA acts on the same receptor which binds marihuana active derivatives, this group of compounds were called endocannabinoids. Besides typical central effects of cannabinoids, CB1 receptor activation leads to hyperphagia, whereas its pharmacological blockade is followed by changes in energy metabolism favouring substrate oxidation. OEA has inhibitory effects on food intake by acting on PPARalpha receptors which modulate the autonomous nervous system. Both acylethanolamides, AEA and OEA, have opposite effects suggesting that they form part of a satiety sensor system. Whereas fasting triggers AEA release and inhibits OEA synthesis, eating has the reverse effect. Additionally OEA is also produced by adipocytes ad has some effects on lipid metabolism. All these data suggest a role for acylethanolamides and the endocannabinoid system in the pathophysiology of obesity, diabetes and atherosclerosis.
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PMID:[The endocannabinoid system and food intake control]. 1538 9

We investigated the effects of chronic treatment with the CB1 receptor antagonist rimonabant (10 mg/kg/day p.o. for 10 weeks) in mice with established obesity (5-month high-fat diet). Untreated obese mice showed a weight gain of 46% (45.0 +/- 0.6 g vs. 30.8 +/- 0.5 g) compared with age-matched animals fed a standard diet. Rimonabant treatment, commencing after 5-month high-fat diet, produced a marked and sustained decrease in body weight (34.5 +/- 0.8 g vs. 47.2 +/- 0.5 g in the high-fat vehicle group, p < 0.001). The anti-obesity effect of rimonabant was similar to that obtained by switching obese mice from high-fat diet to standard laboratory diet during 10 weeks (final weight 33.7 +/- 0.6 g) and was associated with only transient (14 days) reduction in energy intake. Serum leptin, insulin and glucose levels were markedly elevated in obese animals. Rimonabant treatment significantly reduced these elevations (leptin -81%, insulin -78%, glucose -67%, p < 0.001 in all cases vs. high-fat vehicle group). In addition, rimonabant treatment modestly but significantly increased serum adiponectin levels (+18%, p < 0.05 vs. high-fat vehicle group). Obese mice demonstrated abnormal serum lipid profiles. Although rimonabant did not modify high-density lipoprotein cholesterol (HDLc) and had modest effects on total cholesterol, it significantly reduced triglycerides and low-density lipoprotein cholesterol (LDLc) and, notably, increased the HDLc/LDLc ratio (12.4 +/- 0.8 vs. 7.9 +/- 0.2 in high-fat vehicle group, p < 0.001). Therefore, in a model of established obesity, chronic rimonabant treatment produces a marked and sustained decrease in body weight (equivalent to that achieved by dietary change) which is associated with favourable modifications in serum biochemical and lipid profiles.
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PMID:The anti-obesity effect of rimonabant is associated with an improved serum lipid profile. 1564 77

We investigated the molecular events involved in the long-lasting reduction of adipose mass by the selective CB1 antagonist, SR141716. Its effects were assessed at the transcriptional level both in white (WAT) and brown (BAT) adipose tissues in a diet-induced obesity model in mice. Our data clearly indicated that SR141716 reversed the phenotype of obese adipocytes at both macroscopic and genomic levels. First, oral treatment with SR141716 at 10 mg/kg/d for 40 days induced a robust reduction of obesity, as shown by the 50% decrease in adipose mass together with a major restoration of white adipocyte morphology similar to lean animals. Second, we found that the major alterations in gene expression levels induced by obesity in WAT and BAT were mostly reversed in SR141716-treated obese mice. Importantly, the transcriptional patterns of treated obese mice were similar to those obtained in the CB1 receptor knockout mice fed a high-fat regimen and which are resistant to obesity, supporting a CB1 receptor-mediated process. Functional analysis of these modulations indicated that the reduction of adipose mass by the molecule resulted from an enhanced lipolysis through the induction of enzymes of the beta-oxidation and TCA cycle, increased energy expenditure, mainly through futile cycling (calcium and substrate), and a tight regulation of glucose homeostasis. These changes accompanied a significant cellular remodeling and contributed to a reduction of the obesity-related inflammatory status. In addition to a transient reduction of food consumption, increases of both fatty acid oxidation and energy expenditure induced by the molecule summate leading to a sustained weight loss. Altogether, these data strongly indicate that the endocannabinoid system has a major role in the regulation of energy metabolism.
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PMID:The CB1 receptor antagonist rimonabant reverses the diet-induced obesity phenotype through the regulation of lipolysis and energy balance. 1600 4

The endocannabinoids are endogenous lipids capable of binding to both cannabinoid receptors (CB) CB1 and CB2. These receptors belong to the G protein-coupled family receptors and they were discovered while investigating the mode of action of ?(9)-tetrahydrocannabinol, a component of Cannabis sativa, to which they bind with high affinity. Among many other brain sites, CB1 is present in the hypothalamic nuclei involved in the control of energy balance and body weight, as well as in neurons of the mesolimbic system which is believed to mediate the incentive value of food. At central nervous system level, CB1 activation is necessary to induce food intake after a short period of food deprivation, and when CB1 is activated by endocannabinoids produced in situ, a stimulation of the ingestion of palatable food has been described. CB1 stimulation leads to modulation of the release of some hypothalamic anorexigenic and orexigenic mediators, as well as of dopamine in the nucleus accumbens shell. Recent evidence has proved that CB1 is also present in the peripheral organs, such as the adipose tissue and gastrointestinal system, key organs in the regulation of energy metabolism. Animal models have provided solid evidence that genetically induced obesity leads to long-lasting overstimulation of endocannabinoid system synthesis resulting in permanent overactivation of CB1, which may then contribute to the maintenance of this disease. Importantly, at peripheral level, CB1 activation has been shown to stimulate lipogenesis in adipocytes. CB1 blockers increase adiponectin production in adipocytes, which leads to increased fatty acid oxidation and free fatty acid clearance. Moreover, CB1 has been shown to be up-regulated in adipocytes derived from obese rodents. These results support the role of endocannabinoids in the development and maintenance of obesity, paving the way for the development of a new class of drugs such as the CB1 blockers as a therapy for tackling obesity and the associated major cardiovascular risk factors.
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PMID:The endocannabinoid system and the treatment of obesity. 1601 25


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