Triazole GHS-R1a antagonists JMV4208 and JMV3002 attenuate food intake, body weight, and adipose tissue mass in mice
| Autor: | fehrentz, jean-alain, Holubova, M., Nagelová, V., Lacinova, Z., Haluzik, M., Sýkora, D., Moulin, A., Blayo, A.L., Fehrentz, J.A., Martinez, J., Stofkova, A., Jurčovičová, J., Železná, B., Maletinska, L. |
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| Přispěvatelé: | Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB / CAS), Czech Academy of Sciences [Prague] (CAS), 1st Faculty of Medicine, Charles University and General University Hospital, Chimie et Photonique Moléculaires (CPM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Instituto Nacional de Técnica Aeroespacial (INTA), Institute of Experimental Endocrinology, Slovak Academy of Science [Bratislava] (SAS) |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
Adipose tissue Biochemistry Eating Mice Endocrinology Orexigenic Internal medicine medicine Animals Receptor Picolinic Acids Receptors Ghrelin Molecular Biology ComputingMilieux_MISCELLANEOUS 2. Zero hunger biology Dose-Response Relationship Drug business.industry Leptin Body Weight Triazoles medicine.disease Obesity 3. Good health Mice Inbred C57BL Fatty acid synthase Adipose Tissue biology.protein Ghrelin business [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition Hormone medicine.drug |
| Zdroj: | Molecular and Cellular Endocrinology Molecular and Cellular Endocrinology, Elsevier, 2014, 393 (1-2), pp.120-128. ⟨10.1016/j.mce.2014.06.003⟩ |
| ISSN: | 0303-7207 |
| Popis: | The only peripherally released orexigenic hormone, ghrelin, plays a key role in food intake and body weight regulation. Antagonizing the ghrelin receptor, GHS-R1a, represents a promising approach for anti-obesity therapy. In our study, two novel GHS-R1a antagonists JMV4208 and JMV3002, which are trisubstituted 1,2,4-triazoles, decreased food intake in fasted lean mice in a dose-dependent manner, with ED 50 values of 5.25 and 2.05 mg/kg, respectively. Both compounds were stable in mouse blood, with half-lives of 90 min (JMV4208) and 60 min (JMV3002), and disappeared from the blood 8 h after administration. Fourteen days of treatment with the ghrelin antagonists (20 mg/kg twice a day) decreased food intake, body weight and adipose tissue mass in mice with diet-induced obesity (DIO). These results are likely attributable to an impact on food intake reduction and an attenuated expression of the lipogenesis-promoting enzymes (acetyl-CoA carboxylase 1 in subcutaneous fat and fatty acid synthase in subcutaneous and intraperitoneal fat). The decrease in fat mass negatively impacted circulating leptin levels. These data suggest that JMV4208 and JMV3002 could be useful therapeutic agents for the treatment of obesity. |
| Databáze: | OpenAIRE |
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