Endoplasmic reticulum stress and renal lesion in mice with combination of high-fat diet and streptozotocin-induced diabetes

Abstract

PURPOSE:To investigate in the kidney the pathologic changes and expression of GRP78 and CHOP in the Kunming (KM) mice with combination of high-fat diet and streptozotocin-induced diabetes. METHODS:Sixty two male KM mice were randomly divided into a normal control (NC) group (n=20) and a high-fat diet (HFD) group (n=42). After a four-week dietary manipulation, the KM mice in the HFD group were injected intraperitoneally with streptozotocin to induce diabetes. After diabetic models were successfully established, the kidneys were excised and conserved for further test. RESULTS:No significant difference in the body weight was observed after the dietary manipulation (p=0.554). After the streptozotocin was injected, fasting blood glucose levels in the diabetes group (DM) were significantly higher than that in the NC group (p<0.0001).Glomerular atrophy observed under light microscope in the DM group was more serious compared with the NC group. The expression of GRP78 and CHOP in the kidneys of the mice in the DM group were higher compared with the NC group. CONCLUSION:Renal lesion occurs in the diabetic Kunming mice induced by combination of high-fat diet and low-dose streptozotocin, and endoplasmic reticulum stress and CHOP may contribute to the injury process.

Diabetic nephropathy in mice is aggravated by the absence of podocyte IRE1 and is correlated with reduced kidney ADH1 expression

“…The endoplasmic reticulum (ER) plays a critical role in protein folding, lipid synthesis, and calcium storage and release (1). Acute nutrient excess or obesity leads to the development of ER stress, triggering the activation of a group of signaling pathways, termed the unfolded protein response (UPR), in the liver, kidneys (2), and other organs. Three ER-stress-activated enzymesinositol-requiring enzyme 1 (IRE1α), PKR-like ER kinase (PERK), and activating transcription factor 6 (ATF6)together maintain ER homeostasis by activating distinct branches of the UPR.…”

Effect of feeding high fat diets differing in fatty acid composition on oxidative stress markers and protein expression in mouse kidney

“…The results of the current study also demonstrated a decreased expression of two chaperones, namely HSPA5 and HSPD1, in the kidneys of the HR-and SFA-fed animals, respectively. This phenomenon is difficult to explain in light of the significant induction of endoplasmic reticulum stress caused by the administration of HFDs recorded in other studies (Xie et al, 2016;Sánchez-Navarro et al, 2021).…”

Huaju Xiaoji Formula Regulates ERS-lncMGC/miRNA to Enhance the Renal Function of Hypertensive Diabetic Mice with Nephropathy

“…GRP78 facilitates the proper folding of de novo proteins and regulates the unfolded protein response to control ERS in the ER [52]. In Kunming mice, a combination treatment of a high-fat diet with STZ was found to upregulate the expression of CHOP and GRP78 in the kidneys [53]. In our study, an increase in the expression of CHOP and GRP78 was observed in mice induced by STZ-LNAME and model HGMCs, but HJXJ treatment decreased the expression of CHOP and GRP78.…”