title: JTT-130, a novel intestine-specific inhibitor of microsomal triglyceride transfer protein, reduces food preference for fat.
abstract: Microsomal triglyceride transfer protein (MTP) is involved in the assembly and secretion of triglyceride-rich lipoproteins from enterocytes and hepatocytes. JTT-130 is a novel intestine-specific MTP inhibitor, which has been shown to be useful in the prevention and treatment of dyslipidemia, obesity, and diabetes. JTT-130 has also been shown to suppress food intake in a dietary fat-dependent manner in rats. However, whether JTT-130 enables changes in food preference and nutrient consumption remains to be determined. Therefore, the aim of the present study was to investigate the effects of JTT-130 on food preference in rat under free access to two different diets containing 3.3% fat (low-fat diet, LF diet) and 35% fat (high-fat diet, HF diet). JTT-130 decreased HF diet intake and increased LF diet intake, resulting in a change in ratio of caloric intake from LF and HF diets to total caloric intake. In addition, macronutrient analysis revealed that JTT-130 did not affect carbohydrate consumption but significantly decreased fat consumption (P < 0.01). These findings suggest that JTT-130 not only inhibits fat absorption, but also suppresses food intake and specifically reduces food preference for fat. Therefore, JTT-130 is expected to provide a new option for the prevention and treatment of obesity and obesity-related metabolic disorders.
authors: Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
authors: Yasuko
authors: 0000-0003-1592-4655
authors: Y
authors: Mera
authors: Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
authors: Takahiro
authors: T
authors: Hata
authors: Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
authors: Yukihito
authors: Y
authors: Ishii
authors: Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
authors: Daisuke
authors: D
authors: Tomimoto
authors: Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
authors: Takashi
authors: T
authors: Kawai
authors: Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
authors: Takeshi
authors: T
authors: Ohta
authors: Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
authors: Makoto
authors: 0000-0003-3729-296X
authors: M
authors: Kakutani
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001835:Body Weight; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D059305:Diet, High-Fat; D004041:Dietary Fats; D004435:Eating; D002149:Energy Intake; D005247:Feeding Behavior; D005518:Food Preferences; D007422:Intestines / Q000187:drug effects*; D008297:Male; D008314:Malonates / Q000494:pharmacology*; D009765:Obesity / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D015430:Weight Gain
chemical_list: D001549:Benzamides; D002352:Carrier Proteins; D004041:Dietary Fats; D008314:Malonates; C556241:diethyl 2-((3-dimethylcarbamoyl-4-((4'-trifluoromethylbiphenyl-2-carbonyl)amino)phenyl)acetyloxymethyl)-2-phenylmalonate; C106092:microsomal triglyceride transfer protein