Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
, 336 (3), 850-6

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

Affiliations
Comparative Study

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

Takahiro Hata et al. J Pharmacol Exp Ther.

Erratum in

  • J Pharmacol Exp Ther. 2011 Mar;336(3):321-2

Abstract

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.

Similar articles

See all similar articles

Cited by 11 articles

See all "Cited by" articles

Publication types

Substances

LinkOut - more resources

Feedback