Alterations of LXRalpha and LXRbeta expression in the hypothalamus of glucose-intolerant rats.

KRUSE, M.S.; REY, M.; VEGA, M.C.; COIRINI, H.

JOURNAL OF ENDOCRINOLOGY

BIOSCIENTIFICA LTD

Lugar: Bristol; Año: 2012 vol. 215 p. 51 - 58

0022-0795

Liver X receptor (LXR) alpha and beta are nuclear receptors that are crucial for the regulation of the carbohydrate and lipid metabolisms. Activation of LXRs in the brain facilitates cholesterol clearance and improves cognitive deficits, thus they are considered as promising drug targets to treat diseases such as atherosclerosis and Alzheimer´s disease. Nevertheless, little is known about the function and localization of LXRs in the brain. Here, we studied the expression of LXR in the brains of rats that received free access to 10 % (w/v) fructose group (FG) in the beverages or water control drinks (control group (CG). After 6 weeks FG presented hypertriglyceridemia, hyperinsulinemia and became glucose intolerant, suggesting a progression towards type 2 diabetes. We found that hypothalamic LXR expression was altered in fructose fed-rats. Rats in the FG presented a decrease of LXR beta levels while showing an increase in LXR alpha expression in the hypothalamus but not in the hippocampus, cerebellum or neocortex. Moreover, both LXR alpha and beta expression correlated negatively with insulin and triglyceride levels. Interestingly, LXR beta  showed a negative correlation with the area under the curve during the glucose tolerance test in CG, and a positive correlation in FG. Immunocytochemistry revealed that the paraventricular and ventromedial nuclei express mainly LXR alpha whereas the arcuate nucleus expresses LXR beta . Both LXR immunosignals were found in the median preoptic area. This is the first study showing a relationship between glucose and lipid homeostasis and the expression of LXRs in the hypothalamus, suggesting that LXRs may trigger neurochemical and neurophysiological responses for the control of food intake and energy expenditure through these receptors.