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http://hdl.handle.net/10261/61698
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dc.contributor.author | Alonso, M. | - |
dc.contributor.author | Serrano, A. | - |
dc.contributor.author | Vida, M. | - |
dc.contributor.author | Crespillo, A | - |
dc.contributor.author | Hernández-Folgado, Laura | - |
dc.contributor.author | Jagerovic, Nadine | - |
dc.contributor.author | Goya, Pilar | - |
dc.contributor.author | Reyes-Cabello, C. . | - |
dc.contributor.author | Pérez-Valero, V. | - |
dc.contributor.author | Decara, Juan | - |
dc.contributor.author | Macías-González, Manuel | - |
dc.contributor.author | Bermúdez-Silva, Francisco Javier | - |
dc.contributor.author | Suárez, J. | - |
dc.contributor.author | Rodríguez de Fonseca, Fernando | - |
dc.contributor.author | Pavón, Francisco Javier | - |
dc.date.accessioned | 2012-12-03T10:32:19Z | - |
dc.date.available | 2012-12-03T10:32:19Z | - |
dc.date.issued | 2012 | - |
dc.identifier | doi: 10.1111/j.1476-5381.2011.01698.x | - |
dc.identifier | issn: 0007-1188 | - |
dc.identifier.citation | British Journal of Pharmacology 165: 2274- 2291 (2012) | - |
dc.identifier.uri | http://hdl.handle.net/10261/61698 | - |
dc.description.abstract | BACKGROUND AND PURPOSE Peripheral blockade of cannabinoid CB 1 receptors has been proposed as a safe and effective therapy against obesity, putatively devoid of the adverse psychiatric side effects of centrally acting CB 1 receptor antagonists. In this study we analysed the effects of LH-21, a peripherally acting neutral cannabinoid receptor antagonist with poor brain penetration, in an animal model of diet-induced obesity. EXPERIMENTAL APPROACH To induce obesity, male Wistar rats were fed a high-fat diet (HFD; 60 kcal% fat) whereas controls received a standard diet (SD; 10 kcal% fat). Following 10 weeks of feeding, animals received a daily i.p. injection of vehicle or 3 mg·kg -1 LH-21 for 10 days. Plasma and liver samples were used for biochemical analyses whereas visceral fat-pad samples were analysed for lipid metabolism gene expression using real-time RT-PCR. In addition, the potential of LH-21 to interact with hepatic cytochrome P450 isoforms and cardiac human Ether-à-go-go Related Gene (hERG) channels was evaluated. KEY RESULTS LH-21 reduced feeding and body weight gain in HFD-fed animals compared with the control group fed SD. In adipose tissue, this effect was associated with decreased gene expression of: (i) leptin; (ii) lipogenic enzymes, including SCD-1; (iii) CB 1 receptors; and (iv) both PPARα and PPARγ. Although there were no significant differences in plasma parameters between HFD- and SD-fed rats, LH-21 did not seem to induce hepatic, cardiac or renal toxicity. CONCLUSIONS AND IMPLICATIONS These results support the hypothesis that treatment with the peripherally neutral acting CB 1 receptor antagonist, LH-21, may promote weight loss through modulation of visceral adipose tissue. © 2011 The Authors. British Journal of Pharmacology. | - |
dc.language.iso | eng | - |
dc.publisher | Nature Publishing Group | - |
dc.rights | closedAccess | - |
dc.title | Anti-obesity efficacy of LH-21, a cannabinoid CB 1 receptor antagonist with poor brain penetration, in diet-induced obese rats | - |
dc.type | artículo | - |
dc.identifier.doi | 10.1111/j.1476-5381.2011.01698.x | - |
dc.date.updated | 2012-12-03T10:32:20Z | - |
dc.description.version | Peer Reviewed | - |
dc.identifier.pmid | 21951309 | - |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.openairetype | artículo | - |
item.grantfulltext | none | - |
item.cerifentitytype | Publications | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | No Fulltext | - |
item.languageiso639-1 | en | - |
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