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Triazole GHS-R1a antagonists JMV4208 and JMV3002 attenuate food intake, body weight, and adipose tissue mass in mice.
Holubová, M; Nagelová, V; Lacinová, Z; Haluzík, M; Sýkora, D; Moulin, A; Blayo, A L; Fehrentz, J A; Martinez, J; Stofkova, A; Jurcovicová, J; Zelezná, B; Maletínská, L.
Afiliación
  • Holubová M; Institute of Organic Chemistry and Biochemistry, AS CR, Prague, Czech Republic; Third Department of Medicine, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
  • Nagelová V; Institute of Organic Chemistry and Biochemistry, AS CR, Prague, Czech Republic.
  • Lacinová Z; Third Department of Medicine, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
  • Haluzík M; Third Department of Medicine, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
  • Sýkora D; Institute of Chemical Technology, Department of Analytical Chemistry, Prague, Czech Republic.
  • Moulin A; IBMM UMR 5274, CNRS - Universités Montpellier 1- Montpellier 2, Faculté de Pharmacie, Montpellier, France.
  • Blayo AL; IBMM UMR 5274, CNRS - Universités Montpellier 1- Montpellier 2, Faculté de Pharmacie, Montpellier, France.
  • Fehrentz JA; IBMM UMR 5274, CNRS - Universités Montpellier 1- Montpellier 2, Faculté de Pharmacie, Montpellier, France.
  • Martinez J; IBMM UMR 5274, CNRS - Universités Montpellier 1- Montpellier 2, Faculté de Pharmacie, Montpellier, France.
  • Stofkova A; Department of Normal, Pathological and Clinical Physiology, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
  • Jurcovicová J; Department of Normal, Pathological and Clinical Physiology, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
  • Zelezná B; Institute of Organic Chemistry and Biochemistry, AS CR, Prague, Czech Republic.
  • Maletínská L; Institute of Organic Chemistry and Biochemistry, AS CR, Prague, Czech Republic. Electronic address: maletin@uochb.cas.cz.
Mol Cell Endocrinol ; 393(1-2): 120-8, 2014 Aug 05.
Article en En | MEDLINE | ID: mdl-24953973
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 ED50 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 8h 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ácidos Picolínicos / Triazoles / Peso Corporal / Tejido Adiposo / Ingestión de Alimentos / Receptores de Ghrelina Límite: Animals Idioma: En Revista: Mol Cell Endocrinol Año: 2014 Tipo del documento: Article País de afiliación: República Checa Pais de publicación: Irlanda
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ácidos Picolínicos / Triazoles / Peso Corporal / Tejido Adiposo / Ingestión de Alimentos / Receptores de Ghrelina Límite: Animals Idioma: En Revista: Mol Cell Endocrinol Año: 2014 Tipo del documento: Article País de afiliación: República Checa Pais de publicación: Irlanda