Endoplasmic reticulum stress and unfolded protein response in renal lipid metabolism

The endoplasmic reticulum (ER) is a crucial cellular organelle involved in protein synthesis, folding, modification, and transport. Exposure to internal and external stressors can induce endoplasmic reticulum stress (ERS), leading to abnormal protein folding and ER malfunction. This stress can disrupt lipid synthesis, metabolism, and transport processes. Fatty acid oxidation is the primary energy source for the renal system. When energy intake exceeds the storage capacity of adipose tissue, lipids accumulate abnormally in non-adipose tissues, including kidneys, liver, and pancreas. Lipids accumulate in the kidneys of nearly all cell types, including thylakoid membranous, pedunculated, and proximal renal tubular epithelial cells. Intracellular free fatty acids can significantly disrupt renal lipid metabolism, contributing to ischemia-reperfusion acute kidney injury, diabetic nephropathy, renal fibrosis, and lupus nephritis. Consequently, this study delineated the primary signaling pathways and mechanisms of the ERS-induced unfolded protein response, explored the mechanistic link between ERS and lipid metabolism, and elucidated its role in renal lipid metabolism. This study aimed to offer new perspectives on managing and treating renal disorders.