Ipragliflozin, an SGLT2 inhibitor, exhibits a prophylactic effect on hepatic steatosis and fibrosis induced by choline-deficient L-amino acid-defined diet in rats
Ipragliflozin, an SGLT2 inhibitor, exhibits a prophylactic effect on hepatic steatosis and fibrosis induced by choline-deficient L-amino acid-defined diet in rats
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DOI：
10.1016/j.ejphar.2015.02.009
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发表时间：
2015-05-05
影响因子：
5
通讯作者：
Takakura, Shoji
中科院分区：
文献类型：
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作者：
Hayashizaki-Someya, Yuka;Kurosaki, Eiji;Takakura, Shoji
Ipraglivaline是一种选择性钠葡萄糖协同转运蛋白2（SGLT 2）抑制剂，通过抑制肾脏葡萄糖重吸收增加尿糖排泄，从而引起后续的抗高血糖作用。由于非酒精性脂肪性肝病（NAFLD），包括非酒精性脂肪性肝炎（NASH），与肥胖和糖尿病等代谢疾病密切相关，我们研究了伊格列净对喂食胆碱缺乏I的大鼠NAFLD的影响。-氨基酸限定（CDAA）饮食。开始CDAA饮食后5周，大鼠表现出肝脏甘油三酯（TG）蓄积、纤维化和轻度炎症。重复口服伊格列净（3 mg/g，每天一次，持续5周）防止肝TG积累（188对290 mg/g组织载体治疗组; P < 0.001）和大脂滴形成。此外，依格列净对肝纤维化具有预防作用，如羟脯氨酸含量和纤维化评分显著降低所示。已知吡格列酮对喂食CDAA饲料的大鼠以及患有2型糖尿病（T2 DM）的NASH患者的肝纤维化有效，对纤维化也有轻度预防作用，但对肝脏TG蓄积或炎症无预防作用。总之，伊格列净可预防CDAA饮食大鼠的肝脏TG蓄积和纤维化。这些发现表明伊格列净对NAFLD患者的治疗潜力。(C)2015 Elsevier B. V.版权所有。
Ipragliflozin is a selective sodium glucose cotransporter 2 (SGLT2) inhibitor that increases urinary glucose excretion by inhibiting renal glucose reabsorption and thereby causes a subsequent antihyperglycemic effect. As nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), is closely linked to metabolic diseases such as obesity and diabetes, we investigated the effect of ipragliflozin on NAFLD in rats fed a choline-deficient I.-amino acid defined (CDAA) diet. Five weeks after starting the CDAA diet, rats exhibited hepatic triglyceride (TG) accumulation, fibrosis, and mild inflammation. Repeated oral administration of ipragliflozin (3 mg/g, once daily for 5 weeks) prevented both hepatic TG accumulation (188 vs 290 mg/g tissue vehicle treated group; P < 0.001) and large lipid droplet formation. Further, ipragliflozin exerted a prophylactic effect on liver fibrosis, as indicated by a marked decrease in hydroxyproline content and fibrosis score. Pioglitazone, which is known to be effective on hepatic fibrosis in CDAA diet fed rats as well as NASH patients with type 2 diabetes mellitus (T2DM), also exerted a mild prophylactic effect on fibrosis, but not on hepatic TG accumulation or inflammation. In conclusion, ipragliflozin prevented hepatic TG accumulation and fibrosis in CDAA-diet rats. These findings suggest the therapeutic potential of ipragliflozin for patients with NAFLD. (C) 2015 Elsevier B.V. All rights reserved.