| JTT-130, a Novel Intestine-Specific Inhibitor of Microsomal Triglyceride Transfer Protein, Suppresses Food Intake and Gastric Emptying with the Elevation of Plasma Peptide YY and Glucagon-Like Peptide-1 in a Dietary Fat-Dependent Manner. | |
| | |
MedLine Citation:
|
PMID: 21139060 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
|
The microsomal triglyceride transfer protein (MTP) takes part in the mobilization and secretion of triglyceride-rich lipoproteins from enterocytes and hepatocytes. In this study, we investigated the effects of diethyl-2-({3-dimethylcarbamoyl-4-[(4'-trifluoromethylbiphenyl-2-carbonyl) amino] phenyl}acetyloxymethyl)-2-phenylmalonate (JTT-130), a novel intestine-specific MTP inhibitor, on food intake, gastric emptying, and gut peptides using Sprague-Dawley rats fed 3.1% fat, 13% fat, or 35% fat diets. JTT-130 treatment suppressed cumulative food intake and gastric emptying in rats fed a 35% fat diet, but not a 3.1% fat diet. In rats fed a 13% fat diet, JTT-130 treatment decreased cumulative food intake but not gastric emptying. In addition, treatment with orlistat, a lipase inhibitor, completely abolished the reduction of food intake and gastric emptying by JTT-130 in rats fed a 35% fat diet. On the other hand, JTT-130 treatment increased the plasma concentrations of gut peptides, peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) but not cholecystokinin, in the portal vein in rats fed a 35% fat diet. These elevations in PYY and GLP-1 were also abolished by treatment with orlistat. Furthermore, JTT-130 treatment in rats fed a 35% fat diet increased the contents of triglycerides and free fatty acids in the intestinal lumen, which might contribute to the elevation of PYY and GLP-1 levels. The present findings indicate that JTT-130 causes satiety responses, decreased food intake, and gastric emptying in a dietary fat-dependent manner, with enhanced production of gut peptides such as PYY and GLP-1 from the intestine. |
| | |
Authors:
|
Takahiro Hata; Yasuko Mera; Yukihito Ishii; Hironobu Tadaki; Daisuke Tomimoto; Yukiharu Kuroki; Takashi Kawai; Takeshi Ohta; Makoto Kakutani |
Publication Detail:
|
Type: Journal Article Date: 2010-12-07 |
Journal Detail:
|
Title: The Journal of pharmacology and experimental therapeutics Volume: 336 ISSN: 1521-0103 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 2011 Mar |
Date Detail:
|
Created Date: 2011-02-21 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: United States |
Other Details:
|
Languages: eng Pagination: 850-6 Citation Subset: IM |
Affiliation:
|
Japan Tobacco Inc., Central Pharmaceutical Research Institute, 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan. takahiro.hata@jt.com. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Postsynaptic and Presynaptic Group II Metabotropic Glutamate Receptor Activation Reduces Neuronal Ex...
Next Document: Silencing mitogen-activated protein kinase-activated protein kinase-2 arrests inflammatory bone loss...