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

• Published in: Journal of cellular biochemistry 2019-09, Vol.120 (9), p.15211-15221
• Main Authors: Xu, Miao, Jiang, Fei, Li, Bingyan, Zhang, Zengli
• Format: Article
• Language: English
• Subjects: 1,25‐dihydroxyvitamin D3; Accumulation; cholesterol; Clear cell-type renal cell carcinoma; Diabetes; Diabetes mellitus; Diabetic nephropathy; Epithelial cells; Fatty acids; Fatty-acid synthase; feedback response; Glucose; Glucose metabolism; high glucose; lipid droplets; Lipid metabolism; Lipids; Metabolism; Nephropathy; Reductases; Sterol regulatory element-binding protein; Vitamin D3
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.28786

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. 1,25‐Dihydroxyvitamin D3 (1α,25(OH)2D3) markedly increases lipid accumulation in normal medium. High glucose regulates sterol regulatory element‐binding proteins (SREBPs) with feedback regulation and the high glucose–induced activation of SREBPs is suppressed by 1α,25(OH)2D3, suggesting a new opportunity for pharmacological control of 1α,25(OH)2D3 in lipid accumulation.