The effect of cholesterol overload on mouse kidney and kidney-derived cells

Abstract

Introduction: Dyslipidemia is one of the onset and risk factors of chronic kidney disease and renal function drop is seen in lipoprotein abnormal animal models. However, the detailed molecular mechanism of renal lipotoxicity has not been clarified. Therefore, the present study aimed to investigate the influence of cholesterol overload using mouse kidney tissue and kidney-derived cultured cells.Methods: C57BL/6 mice were fed normal diet (ND) or 1.25% cholesterol-containing high-cholesterol diet (HCD) for 11 weeks, and we used megalin as a proximal tubule marker for immunohistology. We added beta-very low density lipoprotein (βVLDL) to kidney-derived cells and examined the effect of cholesterol overload on megalin protein and mRNA expression level, cell proliferation and cholesterol content in cells.Results: In the kidney of HCD mice, the gap between glomerulus and the surrounding Bowman’s capsule decreased and the expression level of megalin decreased. After βVLDL treatment to the cells, the protein expression and mRNA expression level of megalin decreased and cell proliferation was restrained. We also observed an increase in cholesterol accumulation in the cell and free cholesterol/phospholipid ratios increased.Conclusions: These findings suggest that the increased cholesterol load on kidney contribute to the decrease of megalin and the overloaded cholesterol is taken into the renal tubule epithelial cells, causing suppression on cell proliferation, which may be the cause of kidney damage.

PNPLA3 rs738409 is associated with renal glomerular and tubular injury in NAFLD patients with persistently normal ALT levels

“…Therefore, it is reasonable to speculate that PNPLA3 expression in the kidneys might also be stimulated under conditions of lipid excess and then increase ectopic lipid accumulation in renal mesangial and tubular cells. In addition, renal lipotoxicity can also promote kidney tubular impairment, abnormal albuminuria and glomerulosclerosis, thus causing a progressive decline in kidney function (33)(34)(35)(36).…”

Sterol-O-acyltransferase-1 has a role in kidney disease associated with diabetes and Alport syndrome

“…Several studies have investigated the role of cellular lipid accumulation on tubulointerstitial injury and fibrosis. [34][35][36][37] Kang et al 37 demonstrated that the expression of key enzymes and regulators of fatty acid oxidation is decreased, whereas intracellular lipid deposition is increased in humans and in mouse models with tubulointerstitial fibrosis. Others demonstrated that mice fed on a cholesterol/fat-rich diet are characterized by increased accumulation of FC and phospholipids within multilamellar organelles of lysosomal origin in renal proximal tubular epithelial cells.…”

High glucose aggravates lipid deposition in glomerular endothelial cells by LXRs/LncRNAOR13C9/ABCA1 pathway

“…However, the mechanism by which this damage occurs in GEnCs is still In most cells, cholesterol cannot be decomposed or metabolized and can only be maintained by transport of cholesterol out of cells [25]. Lipid accumulation in renal cells is an important feature of high-cholesterol-induced renal injury [26]. Therefore, in GEnCs, when cholesterol overload occurs, the outflow system of cholesterol plays an important role in reducing cell damage caused by high lipid deposition [27].…”