Regulation of the expression of LXR in rat hypothalamic and hippocampal explants.

Liver X receptors (LXR) are important transcription factors involved in the regulation of carbohydrate and lipid metabolism and are expressed in different brain areas. Recently we described that LXR expression in the hypothalamus is sensitive to serum levels of lipids and carbohydrates. Here, we further characterized the effects of glucose, insulin, cholesterol and cholic acid on the expression of LXRα and LXRβ in hypothalamus and hippocampus explants as in vitro models. The LXR activation products, GLUT2 and ABCA1, were also analyzed by Western blot. Glucose had different effects in the hypothalamus compared to the hippocampus. In the hypothalamus, increases in glucose concentrations decreased LXRβ expression while in the hippocampus increased both receptor subtypes levels. In contrast, insulin treatment decreased LXRβ in the hypothalamus while having no effects on the hippocampus. Cholic acid and cholesterol increased only LXRα expression in the hypothalamus whereas no effects on the hippocampus were detected. The newly expressed LXR receptors may be functional active since the level of the LXR activation product ABCA1 was also increased. Changes in GLUT2 expression was observed only when LXRβ levels were increased. Altogether these data show that LXR are sensitive to glucose, insulin and lipids in vitro, as well as in vivo as we previously showed, suggesting an involvement of LXR in central metabolic pathways and control of energy homeostasis.