Alterations of LXRs expression in the hypothalamus of glucose-intolerant rats.

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

Cancun

Congreso; I Congreso FALAN; 2012

The International Society for Neurochemistry and the American Society for Neurochemistry

Liver X receptor (LXR) a and b 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 LXRs brain receptor in rats that received free access to 10 % (w/v) fructose group (FG) in the beverages or water control drinks (CG). After 6 weeks FG presented hypertriglyceridemia, hyperinsulinemia and became glucose intolerant, suggesting a progression towards type 2 diabetes. We found that hypothalamic LXRs expression was altered in fructose fed-rats. FG presented a decrease of LXRb levels while showing an increase in LXRa expression in the hypothalamus but not in the hippocampus, cerebellum or neocortex. Moreover, both LXRa and LXRb expression correlated negatively with insulin and triglyceride levels. Interestingly, LXRb showed a negative correlation with the area under the curve (AUC) during glucose tolerance test in CG, and a positive correlation in FG. Immunocytochemistry revealed that the paraventricular and ventromedial nuclei express mainly LXRa meanwhile the arcuate nucleus express LXRb. Both LXRs 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.