Each liver X receptor (LXR) type has a different purpose in different situations

• Published in: Biochemical and biophysical research communications 2019-01, Vol.508 (1), p.92-96
• Main Authors: Yonezawa, Sei, Abe, Mizuho, Kawasaki, Yasushi, Natori, Yasuhiro, Sugiyama, Akinori
• Format: Article
• Language: English
• Subjects: Kidney; Lipid metabolism; LXR; Nephrosis; Nuclear receptor
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2018.11.076

LXRs, which are nuclear receptors, have 2 isoforms—LXRα and LXRβ. Generally, LXRα is expressed in the liver, kidney, and a limited number of other organs, whereas LXRβ is thought to be expressed ubiquitously. Nevertheless, no clear consensus has been reached on the role of each in kidney lipid metabolism. Many researchers have reported that lipids accumulate in renal tubular epithelial cells during nephrosis. The nephrosis model we used showed the presence of urinary protein 4 days after the induction of illness. Additionally, the model maintained high levels of urinary protein from day 7–14. Lipid accumulation was clearly verified at day 4 and extreme accumulation was observed at day 7. We observed increased expression of LXRα from an early stage of nephrosis. To explore the role of increased LXRα in diseased kidney in vitro, NRK52E, normal kidney tubular epithelial cells, were forced to overexpress LXRα. These cells showed significantly lower lipid accumulation than mock cells did. In contrast, LXRβ knockdown lead to increased lipid accumulation in mock cells, and constancy in overexpressing cells. In normal kidneys, LXRβ is expressed stably to control mainly the intracellular lipids. However, with increasing intracellular lipid accumulation, expression of LXRα and its downstream gene, ABCA1, was upregulated, followed by lipid excretion in an LXRα-dependent manner. This phenomenon strongly suggests the importance of LXRα in lipid metabolism in the diseased kidney. •In the normal kidney, LXRβ plays a role in lipid metabolism.•In the nephrosis kidney, induction of LXRα expression occurs with lipid accumulation.•LXRα regulates lipid metabolism outside the capability of LXRβ in the nephrosis kidney.