Laboratorio de Neurobiología, Instituto de Biología y Medicina Experimental, Vuelta de Obligado 2490, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
J Endocrinol. 2012 Oct;215(1):51-8. doi: 10.1530/JOE-12-0088. Epub 2012 Jul 25.
Liver X receptor (LXR) α and β are nuclear receptors that are crucial for the regulation of carbohydrate and lipid metabolism. 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 their beverages or water control drinks (control group (CG)). After 6 weeks rats in the FG presented with hypertriglyceridemia, hyperinsulinemia, and became glucose intolerant, suggesting a progression toward type 2 diabetes. We found that hypothalamic LXR expression was altered in fructose-fed rats. Rats in the FG presented with a decrease in LXRβ levels while showing an increase in LXRα expression in the hypothalamus but not in the hippocampus, cerebellum, or neocortex. Moreover, both LXRα and β expression correlated negatively with insulin and triglyceride levels. Interestingly, LXRβ showed a negative correlation with the area under the curve during the glucose tolerance test in the CG and a positive correlation in the FG. Immunocytochemistry revealed that the paraventricular and ventromedial nuclei express mainly LXRα whereas the arcuate nucleus expresses LXRβ. 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.
肝 X 受体 (LXR)α 和 β 是核受体，对于调节碳水化合物和脂质代谢至关重要。在大脑中激活 LXR 可促进胆固醇清除并改善认知缺陷，因此它们被认为是治疗动脉粥样硬化和阿尔茨海默病等疾病的有前途的药物靶点。然而，人们对 LXR 在大脑中的功能和定位知之甚少。在这里，我们研究了在自由饮用 10%（w/v）果糖的大鼠（FG）和饮用对照饮料的大鼠（CG）的大脑中 LXR 的表达。6 周后，FG 组大鼠出现高甘油三酯血症、高胰岛素血症和葡萄糖不耐受，表明向 2 型糖尿病进展。我们发现果糖喂养的大鼠下丘脑 LXR 表达发生改变。FG 组大鼠 LXRβ 水平降低，而 LXRα 在下丘脑表达增加，但在海马体、小脑或新皮层则没有。此外，LXRα 和 β 的表达均与胰岛素和甘油三酯水平呈负相关。有趣的是，LXRβ 在 CG 中的葡萄糖耐量试验曲线下面积呈负相关，而在 FG 中呈正相关。免疫细胞化学显示，室旁核和腹内侧核主要表达 LXRα，而弓状核表达 LXRβ。在视前正中核都发现了这两种 LXR 免疫信号。这是第一项研究表明，葡萄糖和脂质稳态与下丘脑 LXR 表达之间存在关系，表明 LXR 可能通过这些受体引发神经化学和神经生理反应，以控制食物摄入和能量消耗。
