Ipragliflozin Ameliorates Endoplasmic Reticulum Stress and Apoptosis through Preventing Ectopic Lipid Deposition in Renal Tubules

International Journal of Molecular Sciences

Marie Yamamoto¹  Kohshiro Hosokawa¹  Tomomitsu Matono¹  Ayami Ida¹  Tsutomu Kanda¹  Takaaki Sugihara¹  Yukari Mae¹  Hajime Isomoto¹  Takuji Iyama¹  Satoko Fukuda¹  Sosuke Taniguchi¹  Tomoaki Takata¹  Masahiko Koda² 

[1] Division of Medicine and Clinical Science, Faculty of Medicine, Tottori University, Yonago, Tottori 683-8504, Japan;Hino Hospital, Hino, Tottori 689-4504, Japan;

关键词: sglt2 inhibitor;    er stress;    lipotoxicity;    steatonephropathy;    ectopic fat accumulation;    nash;    nafld;   

DOI  :  10.3390/ijms21010190

来源: DOAJ

【 摘 要 】

Background: Chronic kidney disease (CKD) and non-alcoholic steatohepatitis (NASH) are major health burdens closely related to metabolic syndrome. A link between CKD and NASH has been assumed; however, the underlying mechanism is still unknown. Ectopic lipid deposition (ELD) in the hepatocyte results in endoplasmic reticulum (ER) stress, which plays an important role in the development of steatohepatitis. ELD is also assumed to play a role in the development of kidney injury. We aimed to investigate the role of ELD and ER stress in the development of CKD, and evaluate the efficacy of a sodium glucose cotransporter-2 inhibitor, ipragliflozin. Methods: Male FLS-ob/ob mice that closely imitate the pathophysiology of NASH were treated with vehicle or ipragliflozin. Metabolic characteristics, histology of the kidney, ER stress, and apoptotic signals were evaluated. Results: The serum triglyceride was significantly lower in mice treated with ipragliflozin. Ipragliflozin reduced ELD in renal tubules. Ipragliflozin also reduced the expression levels of GRP78 and CHOP, apoptotic cells, and interstitial fibrosis. Conclusions: ELD induced kidney injury through ER stress. Ipragliflozin improved the pathogenesis of CKD by reducing ELD and ER stress in NASH-model mice. Our results suggest ipragliflozin has therapeutic effect on CKD in NASH.

【 授权许可】

Unknown