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Atorvastatin attenuates obese-induced kidney injury and impaired renal organic anion transporter 3 function through inhibition of oxidative stress and inflammation.
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ( IF 4.2 ) Pub Date : 2020-02-23 , DOI: 10.1016/j.bbadis.2020.165741 Nattavadee Pengrattanachot 1 , Rada Cherngwelling 1 , Krit Jaikumkao 2 , Anchalee Pongchaidecha 1 , Laongdao Thongnak 1 , Myat Theingi Swe 3 , Varanuj Chatsudthipong 4 , Anusorn Lungkaphin 5
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ( IF 4.2 ) Pub Date : 2020-02-23 , DOI: 10.1016/j.bbadis.2020.165741 Nattavadee Pengrattanachot 1 , Rada Cherngwelling 1 , Krit Jaikumkao 2 , Anchalee Pongchaidecha 1 , Laongdao Thongnak 1 , Myat Theingi Swe 3 , Varanuj Chatsudthipong 4 , Anusorn Lungkaphin 5
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An excessive consumption of high-fat diet can lead to the alterations of glucose and lipid metabolism, impaired insulin signaling and increased ectopic lipid accumulation resulting in renal lipotoxicity and subsequent renal dysfunction. Atorvastatin is a lipid-lowering drug in clinical treatment. Several studies have reported that atorvastatin has several significant pleiotropic effects including anti-inflammatory, antioxidant, and anti-apoptotic effects. However, the effects of atorvastatin on metabolic disturbance and renal lipotoxicity in obesity are not fully understood. In this study, obesity in rat was developed by high-fat diet (HFD) feeding for 16 weeks. After that, the HFD-fed rats were received either a vehicle (HF), atorvastatin (HFA) or vildagliptin (HFVIL), by oral gavage for 4 weeks. We found that HF rats showed insulin resistance, visceral fat expansion and renal lipid accumulation. Impaired renal function and renal organic anion transporter 3 (Oat3) function and expression were also observed in HF rats. The marked increases in MDA level, renal injury and NF-κB, TGF-β, NOX-4, PKC-α expression were demonstrated in HF rats. Atorvastatin or vildagliptin treatment attenuated insulin resistance and renal lipid accumulation-induced lipotoxicity in HFA and HFVIL rats. Moreover, the proteins involved in renal inflammation, fibrosis, oxidative stress and apoptosis were attenuated leading to improved renal Oat3 function and renal function in the treated groups. Interestingly, atorvastatin showed higher efficacy than vildagliptin in improving insulin resistance, renal lipid accumulation and in exerting renoprotective effects in obesity-induced renal injury and impaired renal Oat3 function.
中文翻译：
阿托伐他汀通过抑制氧化应激和炎症减轻了肥胖引起的肾脏损伤和肾有机阴离子转运蛋白3功能受损。
过量摄入高脂饮食会导致葡萄糖和脂质代谢改变，胰岛素信号传导受损以及异位脂质蓄积增加，从而导致肾脏脂质毒性和随后的肾功能障碍。阿托伐他汀是临床治疗中的降脂药物。几项研究报告说，阿托伐他汀具有多种显着的多效作用，包括抗炎，抗氧化剂和抗凋亡作用。但是，阿托伐他汀对肥胖患者代谢紊乱和肾脏脂质毒性的影响尚不完全清楚。在这项研究中，大鼠的肥胖是通过高脂饮食（HFD）喂养16周而引起的。在那之后，喂食HFD的大鼠通过管饲法接受媒介物（HF），阿托伐他汀（HFA）或维格列汀（HFVIL）4周。我们发现HF大鼠表现出胰岛素抵抗，内脏脂肪膨胀和肾脂质蓄积。在HF大鼠中还观察到肾功能受损和肾有机阴离子转运蛋白3（Oat3）功能和表达受损。在HF大鼠中显示出MDA水平，肾损伤和NF-κB，TGF-β，NOX-4，PKC-α表达的显着增加。阿托伐他汀或维格列汀治疗可减轻HFA和HFVIL大鼠的胰岛素抵抗和肾脂质蓄积引起的脂毒性。此外，与肾脏炎症，纤维化，氧化应激和细胞凋亡有关的蛋白质被减弱，从而导致治疗组的肾脏Oat3功能和肾脏功能得到改善。有趣的是，阿托伐他汀在改善胰岛素抵抗方面比维格列汀具有更高的疗效，
更新日期：2020-03-19
中文翻译：
阿托伐他汀通过抑制氧化应激和炎症减轻了肥胖引起的肾脏损伤和肾有机阴离子转运蛋白3功能受损。
过量摄入高脂饮食会导致葡萄糖和脂质代谢改变，胰岛素信号传导受损以及异位脂质蓄积增加，从而导致肾脏脂质毒性和随后的肾功能障碍。阿托伐他汀是临床治疗中的降脂药物。几项研究报告说，阿托伐他汀具有多种显着的多效作用，包括抗炎，抗氧化剂和抗凋亡作用。但是，阿托伐他汀对肥胖患者代谢紊乱和肾脏脂质毒性的影响尚不完全清楚。在这项研究中，大鼠的肥胖是通过高脂饮食（HFD）喂养16周而引起的。在那之后，喂食HFD的大鼠通过管饲法接受媒介物（HF），阿托伐他汀（HFA）或维格列汀（HFVIL）4周。我们发现HF大鼠表现出胰岛素抵抗，内脏脂肪膨胀和肾脂质蓄积。在HF大鼠中还观察到肾功能受损和肾有机阴离子转运蛋白3（Oat3）功能和表达受损。在HF大鼠中显示出MDA水平，肾损伤和NF-κB，TGF-β，NOX-4，PKC-α表达的显着增加。阿托伐他汀或维格列汀治疗可减轻HFA和HFVIL大鼠的胰岛素抵抗和肾脂质蓄积引起的脂毒性。此外，与肾脏炎症，纤维化，氧化应激和细胞凋亡有关的蛋白质被减弱，从而导致治疗组的肾脏Oat3功能和肾脏功能得到改善。有趣的是，阿托伐他汀在改善胰岛素抵抗方面比维格列汀具有更高的疗效，
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