Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Psychiatry, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Neurosci Lett. 2019 Jun 11;703:79-85. doi: 10.1016/j.neulet.2019.03.030. Epub 2019 Mar 19.
Thyrotropin-releasing hormone (TRH) plays an important role in the regulation of energy balance. While the regulation of TRH in the paraventricular nucleus (PVN) in response to changes of energy balance has been well studied, how TRH is regulated in the dorsomedial hypothalamus (DMH) in maintaining energy homeostasis remains unclear. Here, we assessed the effects of food restriction and exercise on hypothalamic Trh expression using Otsuka Long-Evens Tokushima Fatty (OLETF) rats. Sedentary ad lib fed OLETF rats (OLETF-SED) became hyperphagic and obese. These alterations were prevented in OLETF rats with running wheel access (OLETF-RW) or food restriction in which their food was pair-fed (OLETF-PF) to the intake of lean control rats (LETO-SED). Evaluation of hypothalamic gene expression revealed that Trh mRNA expression was increased in the PVN of OLETF-SED rats and normalized in OLETF-RW and OLETF-PF rats compared to LETO-SED rats. In contrast, the expression of Trh in the DMH was decreased in OLETF-SED rats relative to LETO-SED rats. This alteration was reversed in OLETF-RW rats as seen in LETO-SED rats, but food restriction resulted in a significant increase in DMH Trh expression in OLETF-PF rats compared to LETO-SED rats. Strikingly, while Trh mRNA expression was decreased in the PVN of intact rats in response to acute food deprivation, food deprivation resulted in increased expression of Trh in the DMH. Together, these results demonstrate the differential regulation of Trh expression in the PVN and DMH in OLETF rats and suggest that DMH TRH also contributes to hypothalamic regulation of energy balance.
促甲状腺素释放激素(TRH)在能量平衡的调节中起着重要作用。虽然已经很好地研究了能量平衡变化时室旁核(PVN)中 TRH 的调节,但在维持能量稳态时,下丘脑背内侧核(DMH)中 TRH 是如何被调节的仍不清楚。在这里,我们使用 Otsuka Long-Evens Tokushima Fatty(OLETF)大鼠评估了食物限制和运动对下丘脑 Trh 表达的影响。久坐的自由进食 OLETF 大鼠(OLETF-SED)变得暴食和肥胖。这些改变在具有跑步轮通道(OLETF-RW)或食物限制的 OLETF 大鼠中得到了预防,在食物限制中,它们的食物被配给进食(OLETF-PF)给瘦对照大鼠(LETO-SED)的摄入量。下丘脑基因表达评估显示,OLETF-SED 大鼠的 PVN 中 Trh mRNA 表达增加,与 LETO-SED 大鼠相比,OLETF-RW 和 OLETF-PF 大鼠中的表达正常化。相比之下,OLETF-SED 大鼠下丘脑 DMH 中的 Trh 表达减少。这种改变在 OLETF-RW 大鼠中与 LETO-SED 大鼠相似,但与 LETO-SED 大鼠相比,食物限制导致 OLETF-PF 大鼠 DMH 中的 Trh 表达显著增加。引人注目的是,虽然完整大鼠的 PVN 中 Trh mRNA 表达在急性禁食时减少,但禁食导致 DMH 中 Trh 表达增加。总之,这些结果表明 OLETF 大鼠中 PVN 和 DMH 中 Trh 表达的差异调节,并表明 DMH TRH 也有助于能量平衡的下丘脑调节。