The Role of the Unfolded Protein Response on Renal Lipogenesis in C57BL/6 Mice
Open Access
- 7 January 2021
- journal article
- research article
- Published by MDPI AG in Biomolecules
- Vol. 11 (1), 73
- https://doi.org/10.3390/biom11010073
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.Keywords
This publication has 71 references indexed in Scilit:
- Endoplasmic Reticulum and the Unfolded Protein ResponseInternational Review of Cell and Molecular Biology, 2013
- Role of Endoplasmic Reticulum Stress in Metabolic Disease and Other DisordersAnnual Review of Medicine, 2012
- The Unfolded Protein Response: From Stress Pathway to Homeostatic RegulationScience, 2011
- Endoplasmic Reticulum Stress and the Inflammatory Basis of Metabolic DiseaseCell, 2010
- Recent advances in understanding leptin signaling and leptin resistanceAmerican Journal of Physiology-Endocrinology and Metabolism, 2009
- Adaptive suppression of the ATF4–CHOP branch of the unfolded protein response by toll-like receptor signallingNature, 2009
- The CREB coactivator CRTC2 links hepatic ER stress and fasting gluconeogenesisNature, 2009
- Endoplasmic Reticulum Stress Induces Leptin ResistanceMolecular Pharmacology, 2008
- Loss of the Tuberous Sclerosis Complex Tumor Suppressors Triggers the Unfolded Protein Response to Regulate Insulin Signaling and ApoptosisMolecular Cell, 2008
- Signal integration in the endoplasmic reticulum unfolded protein responseNature Reviews Molecular Cell Biology, 2007