Wilkinson Michael, Brown Russell, Imran Syed A, Ur Ehud
Department of Obstetrics and Gynaecology, Dalhousie University, Halifax, N.S., Canada.
Neuroendocrinology. 2007;86(3):191-209. doi: 10.1159/000108635. Epub 2007 Sep 19.
The brain has been recognized as a prominent site of peptide biosynthesis for more than 30 years, and many neuropeptides are now known to be common to gut and brain. With these precedents in mind it is remarkable that adipose-derived peptides like leptin have attracted minimal attention as brain-derived putative neuromodulators of energy balance. This review outlines the evidence that several adipose-specific genes are also expressed in the central nervous system and pituitary gland. We, and others, confirmed that the genes for leptin, resistin, adiponectin, FIAF (fasting-induced adipose factor) and adiponutrin are expressed and regulated in these tissues. For example, leptin mRNA was readily detectable in human, rat, sheep and pig brain, but not in the mouse. Leptin expression in rat brain and pituitary was regulated through development, by food restriction, and following traumatic brain injury. In contrast, hypothalamic resistin mRNA was unaffected by age or by fasting, but was significantly depleted by food restriction in mouse pituitary gland. Similar results were seen in the ob/ob mouse, and we noted a marked reduction in resistin-positive hypothalamic nerve fibres. Resistin and fiaf mRNA were also upregulated in hypoxic/ischaemic mouse brain. Our studies on the regulation of neuronal adipokines were greatly aided by the availability of clonal hypothalamic neuronal cell lines. One of these, N-1, expresses both rstn and fiaf together with several other neuropeptides and receptors involved in energy homeostasis. Selective silencing of rstn revealed an autocrine/paracrine regulatory system, mediated through socs-3 expression that may influence the feedback effects of insulin and leptin in vivo. A similar convergence of signals in the pituitary gland could also influence anterior pituitary hormone secretion. In conclusion, the evidence is suggestive that brain and pituitary-derived adipokines represent a local regulatory circuit that may fine tune the feedback effects of adipose hormones in the control of energy balance.
30多年来，大脑一直被认为是肽生物合成的重要场所，现在已知许多神经肽在肠道和大脑中都很常见。鉴于这些先例，像瘦素这样的脂肪衍生肽作为大脑衍生的假定能量平衡神经调节剂却很少受到关注，这很值得注意。这篇综述概述了一些证据，表明几个脂肪特异性基因也在中枢神经系统和垂体中表达。我们以及其他人证实，瘦素、抵抗素、脂联素、禁食诱导脂肪因子（FIAF）和脂肪营养蛋白的基因在这些组织中表达并受到调节。例如，在人、大鼠、绵羊和猪的大脑中很容易检测到瘦素mRNA，但在小鼠大脑中却检测不到。大鼠大脑和垂体中的瘦素表达在发育过程中、通过食物限制以及创伤性脑损伤后受到调节。相比之下，下丘脑抵抗素mRNA不受年龄或禁食的影响，但在小鼠垂体中因食物限制而显著减少。在ob/ob小鼠中也观察到了类似的结果，并且我们注意到抵抗素阳性的下丘脑神经纤维明显减少。抵抗素和FIAF mRNA在缺氧/缺血的小鼠大脑中也上调。我们对神经元脂肪因子调节的研究因克隆下丘脑神经元细胞系的可用性而得到极大帮助。其中之一，N-1细胞系，同时表达rstn和FIAF以及其他一些参与能量稳态的神经肽和受体。rstn的选择性沉默揭示了一个自分泌/旁分泌调节系统，该系统通过socs-3表达介导，可能会影响体内胰岛素和瘦素的反馈作用。垂体中类似的信号汇聚也可能影响垂体前叶激素的分泌。总之，有证据表明大脑和垂体衍生的脂肪因子代表了一个局部调节回路，可能会在能量平衡控制中微调脂肪激素的反馈作用。
