Yi Chun-Xia, la Fleur Susanne E, Fliers Eric, Kalsbeek Andries
Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands.
Biochim Biophys Acta. 2010 Apr;1802(4):416-31. doi: 10.1016/j.bbadis.2010.01.006. Epub 2010 Jan 11.
Despite a longstanding research interest ever since the early work by Claude Bernard, the functional significance of autonomic liver innervation, either sympathetic or parasympathetic, is still ill defined. This scarcity of information not only holds for the brain control of hepatic metabolism, but also for the metabolic sensing function of the liver and the way in which this metabolic information from the liver affects the brain. Clinical information from the bedside suggests that successful human liver transplantation (implying a complete autonomic liver denervation) causes no life threatening metabolic derangements, at least in the absence of severe metabolic challenges such as hypoglycemia. However, from the benchside, data are accumulating that interference with the neuronal brain-liver connection does cause pronounced changes in liver metabolism. This review provides an extensive overview on how metabolic information is sensed by the liver, and how this information is processed via neuronal pathways to the brain. With this information the brain controls liver metabolism and that of other organs and tissues. We will pay special attention to the hypothalamic pathways involved in these liver-brain-liver circuits. At this stage, we still do not know the final destination and processing of the metabolic information that is transferred from the liver to the brain. On the other hand, in recent years, there has been a considerable increase in the understanding which brain areas are involved in the control of liver metabolism via its autonomic innervation. However, in view of the ever rising prevalence of type 2 diabetes, this potentially highly relevant knowledge is still by far too limited. Thus the autonomic innervation of the liver and its role in the control of metabolism needs our continued and devoted attention.
自克劳德·伯纳德早期的研究工作以来，人们对自主神经对肝脏的支配（无论是交感神经还是副交感神经）一直有着长期的研究兴趣，但自主神经对肝脏支配的功能意义仍未明确界定。这种信息匮乏不仅体现在大脑对肝脏代谢的控制方面，还体现在肝脏的代谢传感功能以及肝脏的这种代谢信息影响大脑的方式上。来自临床床边的信息表明，成功的人体肝脏移植（意味着肝脏完全去自主神经支配）不会导致危及生命的代谢紊乱，至少在没有严重代谢挑战（如低血糖）的情况下如此。然而，从实验台研究来看，越来越多的数据表明，干扰神经元的脑 - 肝连接确实会导致肝脏代谢发生显著变化。这篇综述全面概述了肝脏如何感知代谢信息，以及这些信息如何通过神经元途径传递到大脑进行处理。大脑利用这些信息来控制肝脏以及其他器官和组织的代谢。我们将特别关注参与这些肝 - 脑 - 肝回路的下丘脑途径。在这个阶段，我们仍然不知道从肝脏传递到大脑的代谢信息的最终目的地和处理方式。另一方面，近年来，人们对哪些脑区通过自主神经支配参与肝脏代谢控制的认识有了相当大的提高。然而，鉴于2型糖尿病的患病率不断上升，这种潜在高度相关的知识仍然极为有限。因此，肝脏的自主神经支配及其在代谢控制中的作用需要我们持续且专注的关注。
