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JTT‐130, a novel intestine‐specific inhibitor of microsomal triglyceride transfer protein, suppresses high fat diet‐induced obesity and glucose intolerance in Sprague‐Dawley rats
Author(s) -
Hata T.,
Mera Y.,
Tadaki H.,
Kuroki Y.,
Kawai T.,
Ohta T.,
Kakutani M.
Publication year - 2011
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2011.01368.x
Subject(s) - medicine , endocrinology , microsomal triglyceride transfer protein , triglyceride , obesity , insulin , adipose tissue , type 2 diabetes , chemistry , biology , diabetes mellitus , cholesterol , lipoprotein , very low density lipoprotein
Aim: Microsomal triglyceride transfer protein (MTP) takes part in the mobilization and secretion of triglyceride‐rich lipoproteins from enterocytes and hepatocytes. We investigated the effects of JTT‐130, a novel intestine‐specific MTP inhibitor, on high fat diet‐induced obesity and glucose intolerance. Methods: Male Sprague‐Dawley rats were fed a 3.1% fat diet or a 35% fat diet with or without JTT‐130 as a food admixture (0.029%). Food intake, body weight, abdominal fat, hepatic triglyceride, faecal free fatty acids and plasma levels of glucagon‐like peptide‐1 (GLP‐1) and peptide YY (PYY) were assessed. Plasma levels of glucose and insulin were measured during intraperitoneal glucose tolerance tests. In addition, indirect calorimetry was performed on rats fed with a 35% fat diet. Results: JTT‐130 treatment decreased body weights, abdominal fat and hepatic triglyceride with suppression of food intake and elevation of faecal free fatty acids and plasma GLP‐1 and PYY levels in rats fed with the 35% fat diet, whereas no significant effects on these parameters except for increased faecal free fatty acids were observed in rats fed with the 3.1% fat diet. JTT‐130 treatment decreased plasma levels of glucose and insulin during intraperitoneal glucose tolerance tests on rats fed with the 35% fat diet, but not on rats fed with the 3.1% fat diet. JTT‐130‐treated rats showed increased O 2 consumption and CO 2 production on a 35% fat diet. Conclusions: JTT‐130 suppresses high fat diet‐induced obesity and glucose intolerance with suppression of food intake and fat absorption and could be useful for prevention and treatment of obesity and obesity‐related insulin resistance.