Abstract
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.
Highlights
The kidney injury molecule 1 (Kim-1), an acute injury marker in renal proximal tubules, was analyzed in order to determine if the induced endoplasmic reticulum (ER) stress modified this biomarker
Results from the Kim-1 PCR showed that the low dose of tunicamycin administration significantly increased Kim-1 mRNA expression in the 24 h group, confirming that ER stress induced by tunicamycin caused tubular injury (Figure 1D)
Apoptosis and lipotoxicity have been identified as the three main alterations associated with mesangial expansion, tubular damage and glomerulosclemain alterations associated with mesangial expansion, tubular damage and glomerulorosis
Summary
Recent studies have associated abnormal lipid accumulation in the kidney, known as fatty kidney [1], with kidney disease [1,2,3,4,5]. This abnormality has emerged as a common alteration in chronic kidney diseases and acute kidney injury [6,7,8,9]. Renal damage associated with obesity involves uncontrolled free fatty acid (FFA) release from hypertrophic adipose tissue, where its over-accumulation in renal tissue may induce cellular damage [10,11,12,13]. A study conducted by Biomolecules 2021, 11, 73.
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