Triazole GHS-R1a antagonists JMV4208 and JMV3002 attenuate food intake, body weight, and adipose tissue mass in mice
Jazyk angličtina Země Irsko Médium print-electronic
Typ dokumentu časopisecké články
PubMed
24953973
DOI
10.1016/j.mce.2014.06.003
PII: S0303-7207(14)00177-4
Knihovny.cz E-zdroje
- Klíčová slova
- Diet-induced obesity, Food intake, GHS-R1a antagonists, JMV3002, JMV4208, Male C57BL/6 mice,
- MeSH
- kyseliny pikolinové chemie farmakologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- přijímání potravy účinky léků MeSH
- receptory ghrelinu antagonisté a inhibitory MeSH
- tělesná hmotnost účinky léků MeSH
- triazoly chemie farmakologie MeSH
- tuková tkáň účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- JMV3002 MeSH Prohlížeč
- JMV4208 MeSH Prohlížeč
- kyseliny pikolinové MeSH
- receptory ghrelinu MeSH
- triazoly MeSH
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.
3rd Department of Medicine 1st Faculty of Medicine Charles University Prague Prague Czech Republic
IBMM UMR 5274 CNRS Universités Montpellier 1 Montpellier 2 Faculté de Pharmacie Montpellier France
Institute of Chemical Technology Department of Analytical Chemistry Prague Czech Republic
Institute of Organic Chemistry and Biochemistry AS CR Prague Czech Republic
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