Renal injury observed in several pathologies has been associated with lipid accumulation in the kidney. While it has been suggested that the accumulation of renal lipids depends on free fatty acids released from adipose tissue, it is not known whether in situ renal lipogenesis due to endoplasmic reticulum (ER) stress contributes to kidney injury. The aim of the present study was to elucidate the role of pharmacological ER stress in renal structure and function and its effect on renal lipid metabolism of C57BL/6 mice. ER stress increased serum creatinine and induced kidney structural abnormalities. Tunicamycin-administered mice developed hyperinsulinemia, augmented lipolysis and increased circulating leptin and adiponectin. Renal unfolded protein response (UPR) gene expression markers, the lipogenic transcription factor SREBP1 and the phosphorylation of eIF2α increased 8 h after tunicamycin administration. At 24 h, an increase in BiP protein content was accompanied by a reduction in p-eIF2α and increased SREBP-1 and FASn protein content, in addition to a significant increase in triglyceride content and a reduction in AMPK. Thus, ER stress induces in situ lipid synthesis, leading to renal lipid accumulation and functional alterations. Future pharmacological and/or dietary strategies must target renal ER stress to prevent kidney damage and the progression of metabolic diseases.

中文翻译：

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展开的蛋白应答在C57BL / 6小鼠肾脂质生成中的作用

在几种病理中观察到的肾损伤与脂质在肾脏中的积累有关。尽管已经提出肾脂质的积累取决于从脂肪组织释放的游离脂肪酸，但是尚不知道由于内质网（ER）应激引起的原位肾脂肪形成是否导致肾脏损伤。本研究的目的是阐明药理学内质网应激在肾结构和功能中的作用及其对C57BL / 6小鼠肾脂质代谢的影响。内质网应激增加血清肌酐并诱发肾脏结构异常。给予衣霉素的小鼠发展为高胰岛素血症，脂解增加，循环中的瘦素和脂联素增加。肾未折叠蛋白反应（UPR）基因表达标记，衣霉素给药8 h后，生脂转录因子SREBP1和eIF2α的磷酸化增加。在24小时时，BiP蛋白质含量增加，同时p-eIF2α降低，SREBP-1和FASn蛋白含量增加，此外甘油三酯含量显着增加，AMPK降低。因此，内质网应激引起原位脂质合成，导致肾脂质积聚和功能改变。未来的药理和/或饮食策略必须针对肾脏内质网应激，以防止肾脏损害和代谢疾病的进展。除了甘油三酯含量显着增加和AMPK降低外。因此，内质网应激引起原位脂质合成，导致肾脂质积聚和功能改变。未来的药理和/或饮食策略必须针对肾脏内质网应激，以防止肾脏损害和代谢疾病的进展。除了甘油三酯含量显着增加和AMPK降低外。因此，内质网应激引起原位脂质合成，导致肾脂质积聚和功能改变。未来的药理和/或饮食策略必须针对肾脏内质网应激，以防止肾脏损害和代谢疾病的进展。