Peripheral injections of melanin-concentrating hormone receptor 1 antagonist S38151 decrease food intake and body weight in rodent obesity models
The compound S38151 is a nanomolar antagonist that acts at the melanin-concentrating hormone receptor 1 (MCH1). S38151 is more stable than its purely peptide counterpart, essentially because of the blockade of its N-terminus. Therefore, , its action on various models of obesity was studied. Acute in...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2012-12-01
|
| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fendo.2012.00160/full |
| _version_ | 1819139217860591616 |
|---|---|
| author | Odile eDella-Zuana Valerie eAudinot Viviane eLevenez Alain eKtorza Françoise ePresse Jean-Louis eNahon Jean Albert Boutin |
| author_facet | Odile eDella-Zuana Valerie eAudinot Viviane eLevenez Alain eKtorza Françoise ePresse Jean-Louis eNahon Jean Albert Boutin |
| author_sort | Odile eDella-Zuana |
| collection | DOAJ |
| description | The compound S38151 is a nanomolar antagonist that acts at the melanin-concentrating hormone receptor 1 (MCH1). S38151 is more stable than its purely peptide counterpart, essentially because of the blockade of its N-terminus. Therefore, , its action on various models of obesity was studied. Acute intracerebroventricular (i.c.v.) administration of S38151 in wild-type rats counteracted the effect of the stable precursor of melanin-concentrating hormone (MCH), NEI-MCH, in a dose-dependent manner (from 0.5 to 50 nmol/kg). In genetically obese Zucker fa/fa rats, daily i.c.v. administration of S38151 induced dose-dependent (5, 10, and 20 nmol/kg) inhibition of food intake, water intake, and body weight gain, as well as increased motility (maximal effect observed at 20 nmol/kg). In Zucker fa/fa rats, intraperitoneal injection of S38151 (30 mg/kg) induced complete inhibition of food consumption within 1 h. Daily intraperitoneal injection of S38151 (10 and 30 mg/kg) into genetically obese ob/ob mice or diet-induced obese mice is able to limit body weight gain. Furthermore, S38151 administration (10 and 30 mg/kg) does not affect food intake, water intake, or body weight gain in MCHR1-deleted mice, demonstrating that its effects are linked to its interaction with MCH1. These results validate MCH1 as a target of interest in obesity. S38151 cannot progress to the clinical phase because it is still too poorly stable in vivo. |
| first_indexed | 2024-12-22T11:19:10Z |
| format | Article |
| id | doaj.art-adf31110f4804ea0bc7005a56c3b4716 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-22T11:19:10Z |
| publishDate | 2012-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-adf31110f4804ea0bc7005a56c3b47162022-12-21T18:27:55ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922012-12-01310.3389/fendo.2012.0016036840Peripheral injections of melanin-concentrating hormone receptor 1 antagonist S38151 decrease food intake and body weight in rodent obesity modelsOdile eDella-Zuana0Valerie eAudinot1Viviane eLevenez2Alain eKtorza3Françoise ePresse4Jean-Louis eNahon5Jean Albert Boutin6Institut de Recherches SERVIERInstitut de Recherches SERVIERInstitut de Recherches SERVIERInstitut de Recherches SERVIERCNRSCNRSInstitut de Recherches SERVIERThe compound S38151 is a nanomolar antagonist that acts at the melanin-concentrating hormone receptor 1 (MCH1). S38151 is more stable than its purely peptide counterpart, essentially because of the blockade of its N-terminus. Therefore, , its action on various models of obesity was studied. Acute intracerebroventricular (i.c.v.) administration of S38151 in wild-type rats counteracted the effect of the stable precursor of melanin-concentrating hormone (MCH), NEI-MCH, in a dose-dependent manner (from 0.5 to 50 nmol/kg). In genetically obese Zucker fa/fa rats, daily i.c.v. administration of S38151 induced dose-dependent (5, 10, and 20 nmol/kg) inhibition of food intake, water intake, and body weight gain, as well as increased motility (maximal effect observed at 20 nmol/kg). In Zucker fa/fa rats, intraperitoneal injection of S38151 (30 mg/kg) induced complete inhibition of food consumption within 1 h. Daily intraperitoneal injection of S38151 (10 and 30 mg/kg) into genetically obese ob/ob mice or diet-induced obese mice is able to limit body weight gain. Furthermore, S38151 administration (10 and 30 mg/kg) does not affect food intake, water intake, or body weight gain in MCHR1-deleted mice, demonstrating that its effects are linked to its interaction with MCH1. These results validate MCH1 as a target of interest in obesity. S38151 cannot progress to the clinical phase because it is still too poorly stable in vivo.http://journal.frontiersin.org/Journal/10.3389/fendo.2012.00160/fullFeeding BehaviorMiceratreceptorsmelanin-concentrating hormonepeptide antagonists |
| spellingShingle | Odile eDella-Zuana Valerie eAudinot Viviane eLevenez Alain eKtorza Françoise ePresse Jean-Louis eNahon Jean Albert Boutin Peripheral injections of melanin-concentrating hormone receptor 1 antagonist S38151 decrease food intake and body weight in rodent obesity models Frontiers in Endocrinology Feeding Behavior Mice rat receptors melanin-concentrating hormone peptide antagonists |
| title | Peripheral injections of melanin-concentrating hormone receptor 1 antagonist S38151 decrease food intake and body weight in rodent obesity models |
| title_full | Peripheral injections of melanin-concentrating hormone receptor 1 antagonist S38151 decrease food intake and body weight in rodent obesity models |
| title_fullStr | Peripheral injections of melanin-concentrating hormone receptor 1 antagonist S38151 decrease food intake and body weight in rodent obesity models |
| title_full_unstemmed | Peripheral injections of melanin-concentrating hormone receptor 1 antagonist S38151 decrease food intake and body weight in rodent obesity models |
| title_short | Peripheral injections of melanin-concentrating hormone receptor 1 antagonist S38151 decrease food intake and body weight in rodent obesity models |
| title_sort | peripheral injections of melanin concentrating hormone receptor 1 antagonist s38151 decrease food intake and body weight in rodent obesity models |
| topic | Feeding Behavior Mice rat receptors melanin-concentrating hormone peptide antagonists |
| url | http://journal.frontiersin.org/Journal/10.3389/fendo.2012.00160/full |
| work_keys_str_mv | AT odileedellazuana peripheralinjectionsofmelaninconcentratinghormonereceptor1antagonists38151decreasefoodintakeandbodyweightinrodentobesitymodels AT valerieeaudinot peripheralinjectionsofmelaninconcentratinghormonereceptor1antagonists38151decreasefoodintakeandbodyweightinrodentobesitymodels AT vivianeelevenez peripheralinjectionsofmelaninconcentratinghormonereceptor1antagonists38151decreasefoodintakeandbodyweightinrodentobesitymodels AT alainektorza peripheralinjectionsofmelaninconcentratinghormonereceptor1antagonists38151decreasefoodintakeandbodyweightinrodentobesitymodels AT francoiseepresse peripheralinjectionsofmelaninconcentratinghormonereceptor1antagonists38151decreasefoodintakeandbodyweightinrodentobesitymodels AT jeanlouisenahon peripheralinjectionsofmelaninconcentratinghormonereceptor1antagonists38151decreasefoodintakeandbodyweightinrodentobesitymodels AT jeanalbertboutin peripheralinjectionsofmelaninconcentratinghormonereceptor1antagonists38151decreasefoodintakeandbodyweightinrodentobesitymodels |