非诺贝特能减轻高脂饮食诱发肥胖的未切除肾脏小鼠的肾脏脂肪毒性。

IF 1.3 Q3 UROLOGY & NEPHROLOGY
Barbara Bruna Abreu Castro, Petrus Ferreira Reno, Bianca Fatima Pereira, Kaique Arriel, Fabiana Bastos Bonato, Fernando Antonio Basile Colugnati, Marcos Antonio Cenedeze, Niels Olsen Saraiva-Camara, Helady Sanders-Pinheiro
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引用次数: 0

摘要

简介本研究的目的是探讨非诺贝特(一种过氧化物酶体增殖物激活受体-α激动剂)在肥胖引起的未切除肾脏小鼠肾脏损伤(脂肪毒性)中的作用:方法:对 C57BL/6 小鼠进行肾脏未切除手术和假手术,并喂食正常热量或高脂肪饮食。10 周后,给肥胖小鼠服用 0.02% 非诺贝特 10 周。结果:结果:高脂饮食喂养的小鼠出现了特征性肥胖和高脂血症,随后出现了肾脏脂质积累和损伤,包括肾间质扩张、间质纤维化、炎症和蛋白尿。与肥胖假小鼠相比,未切除肾脏的肥胖小鼠的这些变化更大。非诺贝特治疗可预防高脂血症和肾小球病变,降低脂质积累,改善肾功能障碍,减轻炎症和肾脏纤维化。此外,非诺贝特还能下调肾组织中纤溶酶原激活物抑制剂-1、单核细胞趋化蛋白-1和成纤维细胞生长因子-21的局部表达:结论:非诺贝特激活的过氧化物酶体增殖物激活受体-α以及随后的脂肪分解作用减轻了肾脏脂肪毒性引起的肾小球和肾小管间质病变,从而保护了未切除肾脏的小鼠的肾脏免受肥胖引起的病变的影响。研究结果表明了非诺贝特的药理作用途径,有助于深入了解肥胖导致供肾肾脏损伤的相关机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Fenofibrate attenuates renal lipotoxicity in uninephrectomized mice with high-fat diet-induced obesity.

Introduction: The objective of this study was to investigate the role of fenofibrate, a peroxisome proliferator-activated receptor-α agonist, in obesity-induced kidney damage (lipotoxicity) in mice with uninephrectomy.

Methods: C57BL/6 mice underwent uninephrectomy and sham surgeries and were fed normocaloric or high-fat diets. After 10 weeks, obese mice were administered 0.02% fenofibrate for 10 weeks. Kidney function and morphology were evaluated, as well as levels of inflammatory and fibrotic mediators and lipid metabolism markers.

Results: High-fat diet-fed mice developed characteristic obesity and hyperlipidemia, with subsequent renal lipid accumulation and damage, including mesangial expansion, interstitial fibrosis, inflammation, and proteinuria. These changes were greater in obese uninephrectomy mice than in obese sham mice. Fenofibrate treatment prevented hyperlipidemia and glomerular lesions, lowered lipid accumulation, ameliorated renal dysfunction, and attenuated inflammation and renal fibrosis. Furthermore, fenofibrate treatment downregulated renal tissue expression of plasminogen activator inhibitor-1, monocyte chemoattractant protein-1, and local expression of fibroblast growth factor-21.

Conclusion: Peroxisome proliferator-activated receptor-α activation by fenofibrate, with subsequent lipolysis, attenuated glomerular and tubulointerstitial lesions induced by renal lipotoxicity, thus protecting the kidneys of uninephrectomy mice from obesity-induced lesions. The study findings suggest a pathway in the pharmacological action of fenofibrate, providing insight into the mechanisms involved in kidney damage caused by obesity in kidney donors.

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来源期刊
CiteScore
2.20
自引率
16.70%
发文量
208
审稿时长
16 weeks
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