Department of Human Anatomy and Histoembrology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, China; Xinxiang Key Laboratory of Molecular Neurology, Xinxiang Medical University, Xinxiang 453003, China.
Department of Human Anatomy and Histoembrology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, China; Xinxiang Key Laboratory of Molecular Neurology, Xinxiang Medical University, Xinxiang 453003, China; Henan International Joint Laboratory of Noninvasive Neuromodulation, Xinxiang Medical University, Xinxiang 453003, China.
J Chem Neuroanat. 2021 Nov;117:102016. doi: 10.1016/j.jchemneu.2021.102016. Epub 2021 Aug 26.
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）诱导的能量消耗引起的产热是能量调节的重要方法。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，PVN 中的大量 BDNF 阳性神经元表达多巴胺（DA）受体（DR），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 DR 调节 BDNF 的表达，然后影响 IBAT 的产热。在这项研究中，我们用 6-羟多巴胺（6-OHDA）诱导大鼠双侧 SN 损伤，并通过双免疫荧光和 Western blot 研究了 PVN 中 DR 和 BDNF 的改变表达以及 IBAT 的代谢变化。结果表明，PVN 中的 BDNF 阳性神经元表达 DR1（D1）和 DR2（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 SN 中的 TH 阳性神经元明显减少，TH 表达明显降低，但两组体重、IBAT 重量和食物消耗无差异。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，而脂肪酸合成酶（FAS）的表达减少。6-OHDA 组 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，DR 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。
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