Zhang Chen, Barkholt Pernille, Nielsen Jens Christian, Thorbek Ditte Dencker, Rigbolt Kristoffer, Vrang Niels, Woldbye David Paul Drucker, Jelsing Jacob
Gubra ApS, Hørsholm, Denmark.
Department of Neuroscience, University of Copenhagen, Copenhagen, Denmark.
Brain Res. 2020 Jan 15;1727:146538. doi: 10.1016/j.brainres.2019.146538. Epub 2019 Nov 6.
The surging obesity epidemic calls for a deeper understanding of central nervous system (CNS) mechanisms underlying the biologically defended level of body weight. Here, we analyzed global gene expression in four hypothalamic and two brainstem nuclei involved in energy homeostatic control of body weight in diet-induced obese (DIO) and lean rats. Male Sprague-Dawley rats were offered ad libitum chow, or a two-choice diet consisting of a high palatable high sugar/fat diet and chow for 40 weeks. At termination, the hypothalamic arcuate nucleus (ARC), dorsomedial hypothalamus (DMH), paraventricular nucleus (PVN) and lateral hypothalamus area (LHA), as well as the brainstem area postrema (AP) and nucleus of the solitary tract (NTS), were isolated by laser capture microdissection (LCM) followed by mRNA sequencing. Global gene expression analyses revealed a total of 88 differentially expressed genes (DEGs) in DIO rats. Transcriptome changes were mainly observed in the DMH and NTS and associated with neuropeptide signaling and regulation of signaling transduction pathways, suggesting a key role of these brain regions in body weight regulation.
不断蔓延的肥胖流行趋势要求我们更深入地了解体重生物防御水平背后的中枢神经系统（CNS）机制。在此，我们分析了饮食诱导肥胖（DIO）大鼠和瘦大鼠中参与体重能量稳态控制的四个下丘脑核团和两个脑干核团中的全基因表达情况。雄性Sprague-Dawley大鼠可随意进食普通饲料，或给予由高适口性高糖/高脂饲料和普通饲料组成的二选一饮食，持续40周。实验结束时，通过激光捕获显微切割（LCM）分离出下丘脑弓状核（ARC）、下丘脑背内侧核（DMH）、室旁核（PVN）和下丘脑外侧区（LHA），以及脑干最后区（AP）和孤束核（NTS），随后进行mRNA测序。全基因表达分析显示，DIO大鼠共有88个差异表达基因（DEG）。转录组变化主要在DMH和NTS中观察到，且与神经肽信号传导和信号转导通路的调节有关，这表明这些脑区在体重调节中起关键作用。
