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SGLT2 Inhibition by Empagliflozin Promotes Fat Utilization and Browning and Attenuates Inflammation and Insulin Resistance by Polarizing M2 Macrophages in Diet-induced Obese Mice.
- フォーマット:
- 論文
- 責任表示:
- Xu, Liang ; Nagata, Naoto ; Nagashimada, Mayumi ; Zhuge, Fen ; Ni, Yinhua ; Chen, Guanliang ; Mayoux, Eric ; Kaneko, Shuichi ; Ota, Tsuguhito ; 長田, 直人 ; 金子, 周一 ; 太田, 嗣人
- 言語:
- 英語
- 出版情報:
- Elsevier, 2017-07
- 著者名:
Xu, Liang Nagata, Naoto Nagashimada, Mayumi Zhuge, Fen Ni, Yinhua Chen, Guanliang Mayoux, Eric Kaneko, Shuichi Ota, Tsuguhito 長田, 直人 金子, 周一 太田, 嗣人 - 掲載情報:
- EBioMedicine
- ISSN:
- 2352-3964
- 巻:
- 20
- 開始ページ:
- 137
- 終了ページ:
- 149
- バージョン:
- publisher
- 概要:
- 金沢大学医薬保健研究域医学系<br />Sodium-glucose cotransporter (SGLT) 2 inhibitors increase urinary glucose excretion (UGE), leading to blood glucose reductions and weight loss. However, the impacts of SGLT2 inhibition on energy homeostasis and obe … sity-induced insulin resistance are less well known. Here, we show that empagliflozin, a SGLT2 inhibitor, enhanced energy expenditure and attenuated inflammation and insulin resistance in high-fat-diet-induced obese (DIO) mice. C57BL/6J mice were pair-fed a high-fat diet (HFD) or a HFD with empagliflozin for 16 weeks. Empagliflozin administration increased UGE in the DIO mice, whereas it suppressed HFD-induced weight gain, insulin resistance, and hepatic steatosis. Moreover, empagliflozin shifted energy metabolism towards fat utilization, elevated AMP-activated protein kinase and acetyl-CoA carbolxylase phosphorylation in skeletal muscle, and increased hepatic and plasma fibroblast growth factor 21 levels. Importantly, empagliflozin increased energy expenditure, heat production, and the expression of uncoupling protein 1 in brown fat and in inguinal and epididymal white adipose tissue (WAT). Furthermore, empagliflozin reduced M1-polarized macrophage accumulation while inducing the anti-inflammatory M2 phenotype of macrophages within WAT and liver, lowering plasma TNFα levels and attenuating obesity-related chronic inflammation. Thus, empagliflozin suppressed weight gain by enhancing fat utilization and browning and attenuated obesity-induced inflammation and insulin resistance by polarizing M2 macrophages in WAT and liver. 続きを見る
- URL:
- http://hdl.handle.net/2297/00050482
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