Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jul 27, 2020; 12(7): 350-362
Published online Jul 27, 2020. doi: 10.4254/wjh.v12.i7.350
Ipragliflozin-induced improvement of liver steatosis in obese mice may involve sirtuin signaling
Takayoshi Suga, Ken Sato, Tatsuya Ohyama, Sho Matsui, Takeshi Kobayashi, Hiroki Tojima, Norio Horiguchi, Yuichi Yamazaki, Satoru Kakizaki, Ayaka Nishikido, Takashi Okamura, Masanobu Yamada, Tadahiro Kitamura, Toshio Uraoka
Takayoshi Suga, Ken Sato, Tatsuya Ohyama, Takeshi Kobayashi, Hiroki Tojima, Norio Horiguchi, Yuichi Yamazaki, Satoru Kakizaki, Toshio Uraoka, Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Maebashi 371-8511, Gunma, Japan
Takayoshi Suga, Sho Matsui, Tadahiro Kitamura, Metabolic Signal Research Center, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Gunma, Japan
Ayaka Nishikido, Takashi Okamura, Masanobu Yamada, Department of Medicine and Molecular Science, Gunma Graduate School of Medicine, Maebashi 371-8511, Gunma, Japan
Author contributions: Suga T, Ohyama T, Okamura T, and Nishikido A performed the experiments; Suga T, Sato K, Ohyama T, Matsui S, Kobayashi T, Tojima H, Horiguchi N, Yamazaki Y, Kakizaki S, Kitamura T, and Uraoka T analyzed and interpreted the data; Sato K, Matsui S, and Yamada M gave critical advice; Sato K drafted the article, edited the article, and approved the final version to be published; all authors have read and approved the final manuscript.
Institutional animal care and use committee statement: Approval was obtained from the Gunma University Animal Care and Experimentation Committee and the Gunma University Safety Committee for Recombinant DNA Experiments prior to the experiments under approval numbers 15-016 and 15-030, respectively.
Conflict-of-interest statement: Ipragliflozin was provided by Astellas Pharma, Inc. (Japan). Satoru Kakizaki received lecture fees from Astellas Pharma, Inc. Masanobu Yamada received lecture fees and research funding from Astellas Pharma, Inc., outside the submitted work. Tadahiro Kitamura received research funding from Astellas Pharma, Inc., outside the submitted work.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Ken Sato, MD, PhD, Associate Professor, Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi 371-8511, Gunma, Japan. satoken@gunma-u.ac.jp
Received: February 27, 2020
Peer-review started: February 27, 2020
First decision: April 22, 2020
Revised: May 20, 2020
Accepted: June 2, 2020
Article in press: July 27,2020
Published online: July 27, 2020
Processing time: 146 Days and 17.6 Hours
Core Tip

Core tip: The selective sodium glucose cotransporter 2 inhibitor ipragliflozin significantly ameliorated hepatic lipid accumulation in genetically obese (ob/ob) mice and increased both the mRNA and protein expression levels of sirtuin 1 (SIRT1), a NAD+-dependent protein deacetylase with numerous substrates, in the liver. Ipragliflozin also significantly increased the hepatic mRNA levels of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), peroxisome proliferator-activated receptor α (PPARα), and fibroblast growth factor-21 (FGF21). The liver steatosis-attenuating effects of ipragliflozin in ob/ob mice may have been mediated partly by hepatic SIRT1 signaling, possibly through the PGC-1α/PPARα-FGF21 pathway.