Meng XiangZhi, Zheng RuiPan, Zhang Ying, Qiao MingLiang, Liu Li, Jing Peng, Wang LuLu, Liu Jing, Gao Yan
Department of Human Anatomy, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
J Neurosci Res. 2015 Feb;93(2):350-60. doi: 10.1002/jnr.23488. Epub 2014 Sep 24.
Weight loss is an important nonmotor symptom associated with Parkinson's disease (PD). However, the cellular factors responsible for PD-induced weight loss remain unclear. Because the sympathetic nervous system plays an important role in lipid metabolism and fat cell differentiation, this study investigates whether PD-induced changes to this system are associated with weight loss in a rat model of PD. Body weight and food intake were measured in control and PD-model rats. After 10 weeks, retroperitoneal white adipose tissues (RWAT) were removed and weighed. Markers of the sympathetic nervous system were measured in the brainstem dorsal medulla and RWAT. Free fat acids (FFA), triglycerides (TG), adipocyte differentiation-related genes, and lipolysis-related molecules in the RWAT and serum were analyzed. Differences in body weight and food intake were insignificant in PD-model rats and control rats; however, relative RWAT weight and adipocyte surface area were significantly reduced in the PD group. Changes in markers of the sympathetic nervous system were observed in the brainstem dorsal medulla and RWAT of PD rats. Decreased mRNA expression levels of genes involved in adipocyte differentiation, decreased TG levels in RWAT, increased FFA in RWAT, and increased lipolysis-related molecules in RWAT and serum FFA were observed in PD rats. This study demonstrates that degenerated dopaminergic neurons in the nigrostriatal system correlate with increases in sympathetic nervous system function, resulting in lipolysis and inhibition of fat cell differentiation. These factors ultimately result in the decrease of RWAT in PD-model rats.
体重减轻是帕金森病（PD）相关的重要非运动症状。然而，导致PD引起体重减轻的细胞因素仍不清楚。由于交感神经系统在脂质代谢和脂肪细胞分化中起重要作用，本研究调查了PD引起的该系统变化是否与PD大鼠模型中的体重减轻有关。测量了对照大鼠和PD模型大鼠的体重和食物摄入量。10周后，取出腹膜后白色脂肪组织（RWAT）并称重。测量了脑干背侧延髓和RWAT中交感神经系统的标志物。分析了RWAT和血清中的游离脂肪酸（FFA）、甘油三酯（TG）、脂肪细胞分化相关基因和脂肪分解相关分子。PD模型大鼠和对照大鼠的体重和食物摄入量差异不显著；然而，PD组的相对RWAT重量和脂肪细胞表面积显著降低。在PD大鼠的脑干背侧延髓和RWAT中观察到交感神经系统标志物的变化。在PD大鼠中，观察到脂肪细胞分化相关基因的mRNA表达水平降低、RWAT中的TG水平降低、RWAT中的FFA增加以及RWAT和血清FFA中脂肪分解相关分子增加。本研究表明，黑质纹状体系统中多巴胺能神经元的退化与交感神经系统功能的增加相关，导致脂肪分解和脂肪细胞分化的抑制。这些因素最终导致PD模型大鼠的RWAT减少。
