• Je něco špatně v tomto záznamu ?

Triazole GHS-R1a antagonists JMV4208 and JMV3002 attenuate food intake, body weight, and adipose tissue mass in mice

M. Holubová, V. Nagelová, Z. Lacinová, M. Haluzík, D. Sýkora, A. Moulin, AL. Blayo, JA. Fehrentz, J. Martinez, A. Stofkova, J. Jurčovičová, B. Zelezná, L. Maletínská,

. 2014 ; 393 (1-2) : 120-8.

Jazyk angličtina Země Irsko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc15023314

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.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc15023314
003      
CZ-PrNML
005      
20150729093619.0
007      
ta
008      
150709s2014 ie f 000 0|eng||
009      
AR
024    7_
$a 10.1016/j.mce.2014.06.003 $2 doi
035    __
$a (PubMed)24953973
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a ie
100    1_
$a Holubová, M $u 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.
245    10
$a Triazole GHS-R1a antagonists JMV4208 and JMV3002 attenuate food intake, body weight, and adipose tissue mass in mice / $c M. Holubová, V. Nagelová, Z. Lacinová, M. Haluzík, D. Sýkora, A. Moulin, AL. Blayo, JA. Fehrentz, J. Martinez, A. Stofkova, J. Jurčovičová, B. Zelezná, L. Maletínská,
520    9_
$a 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.
650    _2
$a tuková tkáň $x účinky léků $7 D000273
650    _2
$a zvířata $7 D000818
650    _2
$a tělesná hmotnost $x účinky léků $7 D001835
650    _2
$a vztah mezi dávkou a účinkem léčiva $7 D004305
650    _2
$a přijímání potravy $x účinky léků $7 D004435
650    _2
$a myši $7 D051379
650    _2
$a myši inbrední C57BL $7 D008810
650    _2
$a kyseliny pikolinové $x chemie $x farmakologie $7 D010848
650    _2
$a receptory ghrelinu $x antagonisté a inhibitory $7 D054440
650    _2
$a triazoly $x chemie $x farmakologie $7 D014230
655    _2
$a časopisecké články $7 D016428
700    1_
$a Nagelová, V $u Institute of Organic Chemistry and Biochemistry, AS CR, Prague, Czech Republic.
700    1_
$a Lacinová, Z $u Third Department of Medicine, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
700    1_
$a Haluzík, M $u Third Department of Medicine, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
700    1_
$a Sýkora, D $u Institute of Chemical Technology, Department of Analytical Chemistry, Prague, Czech Republic.
700    1_
$a Moulin, A $u IBMM UMR 5274, CNRS - Universités Montpellier 1- Montpellier 2, Faculté de Pharmacie, Montpellier, France.
700    1_
$a Blayo, A L $u IBMM UMR 5274, CNRS - Universités Montpellier 1- Montpellier 2, Faculté de Pharmacie, Montpellier, France.
700    1_
$a Fehrentz, J A $u IBMM UMR 5274, CNRS - Universités Montpellier 1- Montpellier 2, Faculté de Pharmacie, Montpellier, France.
700    1_
$a Martinez, J $u IBMM UMR 5274, CNRS - Universités Montpellier 1- Montpellier 2, Faculté de Pharmacie, Montpellier, France.
700    1_
$a Stofkova, A $u Department of Normal, Pathological and Clinical Physiology, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
700    1_
$a Jurčovičová, J $u Department of Normal, Pathological and Clinical Physiology, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
700    1_
$a Zelezná, B $u Institute of Organic Chemistry and Biochemistry, AS CR, Prague, Czech Republic.
700    1_
$a Maletínská, L $u Institute of Organic Chemistry and Biochemistry, AS CR, Prague, Czech Republic. Electronic address: maletin@uochb.cas.cz.
773    0_
$w MED00003387 $t Molecular and cellular endocrinology $x 1872-8057 $g Roč. 393, č. 1-2 (2014), s. 120-8
856    41
$u https://pubmed.ncbi.nlm.nih.gov/24953973 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20150709 $b ABA008
991    __
$a 20150729093706 $b ABA008
999    __
$a ok $b bmc $g 1083652 $s 906307
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2014 $b 393 $c 1-2 $d 120-8 $i 1872-8057 $m Molecular and cellular endocrinology $n Mol Cell Endocrinol $x MED00003387
LZP    __
$a Pubmed-20150709

Najít záznam

Citační ukazatele

Možnosti archivace