1α,25(OH)₂D₃ alleviates high glucose–induced lipid accumulation in rat renal tubular epithelial cells by inhibiting SREBPs

Abstract

Lipid accumulation is a vital event in the progression of diabetic nephropathy. 1,25‐Dihydroxyvitamin D3 (1α,25(OH)2D3) is considered to have a protective effect on diabetic nephropathy. However, it remains unclear whether 1α,25(OH)2D3 can inhibit lipid accumulation, and the potential mechanisms responsible for lipid metabolism are incompletely understood. In this study, we evaluated the effects of 1α,25(OH)2D3 on lipid metabolism in high glucose–exposed rat renal tubular epithelial NRK‐52E cells. Results indicated that high glucose–enhanced lipid accumulation in NRK‐52E cells and 1α,25(OH)2D3 can remarkably decrease high glucose–induced lipid accumulation. Western blot showed that 1α,25(OH)2D3 alleviated high glucose–induced upregulation of sterol regulatory element‐binding protein‐1c (SREBP‐1c) and SREBP2, along with their established target genes fatty acid synthase (FASN) and hydroxymethylglutaryl CoA reductases (HMGCR). Overall, these findings suggest that 1α,25(OH)2D3 downregulated the expressions of SREBPs to inhibit high glucose–induced lipid accumulation, which provides new sights into the protective effects of 1α,25(OH)2D3 on diabetic nephropathy.

Analysis of the Glucose-Dependent Transcriptome in Murine Hypothalamic Cells

“…SREBP are encoded by the Srebf1 and Srebf2 genes and are key regulators of cholesterol biosynthesis [ 48 ]. Glucose has been shown to enhance Srebf1 and Srebf2 expression in renal NRK-52E cells, but conversely to inhibit Srebf1 in Schwann cells [ 49 , 50 ]. RNA-seq data obtained with mHypoA-2/10 cells showed that both Srebf genes were upregulated ( Figure 3 C), portending a major role of glucose as a regulator of cholesterol and fatty acid levels by dynamic regulation of Srebf expression.…”

Morroniside Promotes PGC-1α-Mediated Cholesterol Efflux in Sodium Palmitate or High Glucose-Induced Mouse Renal Tubular Epithelial Cells

“…It can enter the cells through free diffusion and active transport, resulting in lipid accumulation in RTECs [ 11 ]. Recent studies have also demonstrated that PA or high glucose (HG) stimulation induces lipid accumulation via lipid synthesis pathways in RTECs [ 12 , 13 ].…”