Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0311277 (abdominal obesity)
 2,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endocannabinoid system, the complex of specific cannabinoid receptors (CB1 and CB2 subtypes) and their endogenous agonistic ligands (endocannabinoids) plays, besides others, an important role in the central and peripheral regulation of food intake, fat accumulation, and lipid and glucose metabolism. Alterations of these functions are associated with endocannabinoid system hyperactivity. The cannabinoid receptor CB1 antagonist rimonabant normalizes the over activated endocannabinoid system which contributes to the regulation of energy homeostasis, and improves lipid and glucose metabolism--decreases body weight, waist circumference, intra-abdominal obesity and triglycerides, increases HDL-C, improves insulin sensitivity according to HOMA index. Results of the international multicentric clinical trials confirm that rimonabant is well tolerated and show antiatherogenic effects (increased adiponectin, decreased marker of inflammation CRP and improvement of LDL profile) as well as decreased percentage of subjects with NCEP/ATPIII (National Cholesterol Education Program Adult Treatment Panel III) defined metabolic syndrome. Thus, the CB1 cannabinoid receptor antagonist rimonabant is suggested to be a prospective drug decreasing cardiometabolic risk factors.
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PMID:[Impact of endocannabinoid system in modulation of cardiometabolic risk factors]. 1687 57

Recent studies have provided evidence that the endocannabinoid (EC) system has very significant effects on energy balance and metabolism through the central control of appetite and by affecting peripheral metabolism. Endocannabinoids are endogenous phospholipid derivatives which bind and activate cannabinoid receptors type 1 and type 2 (CB1 and CB2 receptors). The CB1 receptor, a G-protein coupled receptor, is believed to be responsible for the majority of the central effects of endocannaboids on appetite. Chronic positive energy balance and obesity have been associated with an overactivation of the endocannaboid system which has been suggested to contribute to the development of abdominal obesity and to associated metabolic abnormalities which increase the risk of cardiovascular disease and type 2 diabetes. Animal studies had shown that stimulation of the cannabinoid CB1 receptor with endocannaboids such as anandamide could induce first an increase in food intake leading to body weight gain. Furthermore, an exciting development in this field has been the discovery of CB1 receptors in many peripheral tissues, including key organs involved in carbohydrate and lipid metabolism such as the adipose tissue and liver. Thus, blocking CB1 receptors located in the liver and adipose tissue could have an additional impact on the metabolic risk profile beyond what could be explained by the reduction in food intake and the related body weight loss. Preclinical studies have shown that rimonabant, the first CB1-receptor blocker to be available in clinical practice, could not only induce a reduction in food intake, but could also produce body weight loss beyond what could be explained by its effect on food intake. Thus, the evidence from preclinical studies have suggested that CB1 blockade could represent a relevant approach to reduce food intake, to induce body weight loss, and, most importantly, to "fix" the dysmetabolic state of viscerally obese patients at increased cardiometabolic risk.
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PMID:The endocannabinoid system: a new target for the regulation of energy balance and metabolism. 1766 64

The endocannabinoid system is a complex system with endogenous ligands, synthesis and transport processes, specific receptors (CB1 and CB2) and intracellular degrading enzymes. It is widely distributed in the central nervous system, but also in peripheral organs. In the brain, endocannabinoids and CB1 receptors are almost ubiquitous and play a role in synaptic plasticity: they modulate, through an inhibitory retrograde action, the release of classical neurotransmitters such as amines, acetylcholine or amino acids. They may exert a neuroprotective effect, but are also involved in appetite and alcohol/drug dependence. At the periphery, they are present (and overexpressed in case of abdominal obesity) in various organs involved in energy control and metabolic regulation. Furthermore, CB2 receptors are also present in the brain, although less numerous than CB1 receptors. They could attenuate pain and also be neuroprotective. Selective agonists, antagonists and inverse agonists of CB1 and CB2 receptors are currently developed and open new interesting therapeutic perspectives. Rimonabant, a CB1 antagonist, has been recently launched for the treatment of obese or overweight patients at high cardiometabolic risk.
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PMID:[Endocannabinoid system in the brain...and elsewhere]. 1866 6