Improvement of LXR-mediated lipid metabolism in nephrotic model kidney accompanied by suppression of inflammation and fibrosis

• Published in: Biochemical and biophysical research communications 2023-07, Vol.666, p.122-127
• Main Authors: Yonezawa, Sei, Kawasaki, Yasushi, Natori, Yasuhiro, Sugiyama, Akinori
• Format: Article
• Language: English
• Subjects: Fibrosis; Humans; Inflammation - pathology; Kidney - pathology; Lipid Metabolism; Lipids; Liver X Receptors - metabolism; LXR; Nephrosis; Nuclear receptor; T0901317
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2023.05.019

Kidney disease affects millions of people worldwide. Chronic kidney diseases, such as diabetic nephropathy, are often accompanied by nephrotic syndrome, which causes a large amount of protein and lipid to leak out into the urine. Leaked lipids are well known to accumulate in the proximal tubules as lipid droplets. However, the role of lipid metabolism in the kidney has not been thoroughly studied, and the relationship between accumulated lipid and pathological progression is often unknown. In this study, we showed that reducing accumulated lipids by exerting an agonistic effect on Liver X receptor, one of the nuclear receptors known to play an important role in lipid metabolism, suppressed the development of pathological conditions, such as inflammation and fibrosis, in a nephrosis model. Until now, many renal disease treatments have focused on suppressing the inflammatory response. However, it is now clear that even if the direct anti-inflammatory response is weak, the spread of inflammation and fibrosis can be suppressed by reducing accumulated lipids. Our results suggest that reducing abnormal lipid accumulation in the kidney could lead to disease treatment. •An agonist of upregulated LXRα demonstrated therapeutic effects.•There was no anti-inflammatory effect of LXR agonists on PAN-induced glomerular inflammation.•Suppression of inflammation and fibrosis in tubules with accumulated lipid droplets was accompanied by a decrease in lipids.