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Title: JTP-103237, a monoacylglycerol acyltransferase inhibitor, prevents fatty liver and suppresses both triglyceride synthesis and de novo lipogenesis
Authors: Okuma, Chihiro
Ohta, Takeshi  orcid https://orcid.org/0000-0002-9573-3455 (unconfirmed)
Tadaki, Hironobu
Ishigure, Tatsuya
Sakata, Shohei
Taniuchi, Hideyuki
Sano, Ryuhei
Hamada, Hiromi
Kume, Shinichi  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-8759-8476 (unconfirmed)
Nishiu, Jun
Kakutani, Makoto
Author's alias: 久米, 新一
Keywords: de novo lipogenesis
JTP-103237
Monoacyglycerol acyltransferase
Nonalcoholic fatty liver disease
Issue Date: 9-Apr-2015
Publisher: Japanese Pharmacological Society
Journal title: Journal of Pharmacological Sciences
Volume: 128
Start page: 150
End page: 157
Abstract: Aim Monoacyglycerol acyltransferases (MGATs) are known to play important roles in intestinal TG absorption. In contrast, the role of MGATs in the liver is still unclear. We investigated the effects of JTP-103237, a novel MGAT inhibitor, on hepatic MGAT activity and hepatic lipid metabolism. Results JTP-103237 reduced hepatic triglyceride content and hepatic MGAT activity in a high sucrose very low fat (HSVLF) diet induced fatty liver model. Interestingly, JTP-103237 suppressed not only triglyceride (TG) and diacylglycerol (DG) synthesis, but also fatty acid (FA) synthesis (de novo lipogenesis) in this model. JTP-103237 also suppressed lipogenesis-related gene expression, such as sterol regulatory element-binding protein 1-c. Moreover, JTP-103237 decreased plasma glucose levels and total cholesterol and reduced the accumulation of epididymal fats in HSVLF diet fed mice. Conclusion In the present study, JTP-103237 prevented carbohydrate-induced fatty liver and suppressed both TG synthesis and de novo lipogenesis, suggesting MGAT inhibitor may prevent carbohydrate-induced metabolic disorders, including NAFLD, obesity and diabetes.
Rights: © 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ icenses/by-nc-nd/4.0/).
URI: http://hdl.handle.net/2433/218471
DOI(Published Version): 10.1016/j.jphs.2015.06.007
PubMed ID: 26215699
Appears in Collections:Journal Articles

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