The thermogenesis resulting from brown adipose tissue (BAT)-induced energy consumption is an important method of energy regulation. It has been reported that brain-derived neurotrophic factor (BDNF)-positive neurons in the paraventricular nucleus (PVN) can regulate adaptive thermogenesis in interscapular brown adipose tissue (IBAT), but the upstream regulatory mechanism is still unclear. Our previous studies have found that a large number of dopamine (DA) receptors (DRs) are expressed on BDNF-positive neurons in the PVN and that the substantia nigra (SN) can directly project to the PVN (forming the SN-PVN pathway). Therefore, we speculate that DA in the SN can regulate the expression of BDNF via DRs and then affect IBAT thermogenesis. In this study, bilateral SN lesions were induced in rats with 6-hydroxydopamine (6-OHDA), and the altered expression of DRs and BDNF in the PVN and the metabolic changes in IBAT were studied via double immunofluorescence and western blotting. The results showed that BDNF-positive neurons in the PVN expressed DR 1 (D1) and DR 2 (D2) and were surrounded by a large number of tyrosine hydroxylase (TH)-positive nerve fibers. Compared with the control group, the 6-OHDA group exhibited significantly fewer TH-positive neurons and significantly lower TH expression in the SN, but body weight, IBAT weight and food consumption did not differ between the groups. In the PVN, BDNF expression was upregulated in the 6-OHDA group, while D2 and TH expression was downregulated. In IBAT, the expression of uncoupling protein-1 (UCP-1), phosphorylated hormone-sensitive lipase (p-HSL), TH and β3-adrenergic receptor (β3-AR) was increased, while the expression of fatty acid synthase (FAS) was decreased. The IBAT cell diameter was also decreased in the 6-OHDA group. The results suggest that the SN-PVN pathway may be an upstream neural pathway that can affect BDNF expression in the PVN and that DRs may mediate its regulatory effects. This study expands our understanding of the relationship between DA and obesity.

棕色脂肪组织 (BAT) 诱导的能量消耗产生的产热是一种重要的能量调节方法。据报道，室旁核（PVN）中的脑源性神经营养因子（BDNF）阳性神经元可以调节肩胛间棕色脂肪组织（IBAT）的适应性产热，但上游调节机制尚不清楚。我们之前的研究发现，大量的多巴胺（DA）受体（DRs）在PVN中的BDNF阳性神经元上表达，并且黑质（SN）可以直接投射到PVN（形成SN-PVN通路） . 因此，我们推测SN中的DA可以通过DRs调节BDNF的表达，进而影响IBAT产热。在这项研究中，用 6-羟基多巴胺 (6-OHDA) 诱导大鼠双侧 SN 损伤，通过双重免疫荧光和蛋白质印迹研究PVN中DRs和BDNF的表达改变以及IBAT的代谢变化。结果表明，PVN中BDNF阳性神经元表达DR 1（D1）和DR 2（D2），并被大量酪氨酸羟化酶（TH）阳性神经纤维包围。与对照组相比，6-OHDA组TH阳性神经元显着减少，SN中TH表达显着降低，但体重、IBAT体重和食物消耗在组间没有差异。在PVN中，6-OHDA组BDNF表达上调，而D2和TH表达下调。在 IBAT 中，解偶联蛋白-1 (UCP-1)、磷酸化激素敏感性脂肪酶 (p-HSL)、TH 和 β3-肾上腺素能受体 (β3-AR) 的表达增加，而脂肪酸合酶（FAS）的表达降低。6-OHDA 组的 IBAT 细胞直径也减小。结果表明，SN-PVN通路可能是影响PVN中BDNF表达的上游神经通路，DRs可能介导其调节作用。这项研究扩展了我们对 DA 与肥胖之间关系的理解。