Hillebrand Jacquelien J G, Geary Nori
Forum Nutr. 2010;63:111-122. doi: 10.1159/000264399. Epub 2009 Nov 27.
The physiological regulation of adiposity is supposed to depend on endocrine 'adiposity signals' that inform the brain about the mass of the adipose tissue. Basal levels of insulin and leptin are widely accepted to be adiposity signals, and amylin, ghrelin and peptide YY have been hypothesized to be. Support for these ideas comes from associations between basal hormone levels and levels of adiposity, from demonstrations of receptors for these hormones in neural circuits supposed to regulate energy homeostasis, from neuropharmacological manipulations of the hormones' actions on eating and energy expenditure, and from the effects on energy balance in animals or people bearing mutations in these endocrine signaling pathways. This chapter focuses on only the first of these four types of evidence and only on insulin and leptin. We ask whether circulating levels of either hormone indeed encodes the necessary information to act as an adiposity signal. In considering this question, we emphasize the distinction between regulation of AT mass in steady versus dynamic states. We argue that the best experimental designs for identifying potentially effective adiposity signals involve situations in which the level of adiposity is changing as the organism responds to imposed perturbations. Traditionally, this is the type of design that most convincingly supports the idea that adiposity is actively regulated. Unfortunately, there are few of such studies for any of the hypothesized endocrine adiposity signals, and the evidence that is available does not strongly support the hypotheses. Therefore, we conclude that the question of how adiposity is signaled to the brain remains an open frontier in the physiology of energy homeostasis.
肥胖的生理调节被认为依赖于内分泌“肥胖信号”，这些信号向大脑传递脂肪组织的质量信息。胰岛素和瘦素的基础水平被广泛认为是肥胖信号，并且有人推测胰淀素、胃饥饿素和肽YY也是。对这些观点的支持来自基础激素水平与肥胖程度之间的关联、这些激素在假定调节能量稳态的神经回路中的受体的证明、这些激素对饮食和能量消耗作用的神经药理学操作，以及对这些内分泌信号通路发生突变的动物或人的能量平衡的影响。本章仅关注这四类证据中的第一类，并且仅关注胰岛素和瘦素。我们要问，这两种激素的循环水平是否确实编码了作为肥胖信号所需的信息。在考虑这个问题时，我们强调稳定状态与动态状态下脂肪组织质量调节之间的区别。我们认为，识别潜在有效肥胖信号的最佳实验设计涉及肥胖程度随着生物体对施加的扰动做出反应而变化的情况。传统上，这种设计类型最令人信服地支持了肥胖受到主动调节的观点。不幸的是，对于任何一种假定的内分泌肥胖信号，这类研究都很少，而且现有的证据也没有强有力地支持这些假设。因此，我们得出结论，肥胖如何向大脑发出信号的问题在能量稳态生理学中仍然是一个未被探索的前沿领域。
