Mohamed-Ali V, Pinkney J H, Coppack S W
Department of Medicine, University College London School of Medicine, Whittington Hospital, UK.
Int J Obes Relat Metab Disord. 1998 Dec;22(12):1145-58. doi: 10.1038/sj.ijo.0800770.
The discovery of leptin has imparted great impetus to adipose tissue research by demonstrating a more active role for the adipocyte in energy regulation. Besides leptin, however, the adipose tissue also secretes a large number other signals. Cytokine signals, TNFalpha and IL-6, and components of the alternative pathway of complement influence peripheral fuel storage, mobilization and combustion, as well as energy homeostasis. In addition to the acute regulation of fuel metabolism, adipose tissue also influences steroid conversion and sexual maturation. In this way, adipose tissue is an active endocrine organ, influencing many aspects of fuel metabolism through a network of local and systemic signals, which interact with the established neuroendocrine regulators of adipose tissue. Thus, insulin, catecholamines and anterior pituitary endocrine axes interact at multiple levels with both cytokines and leptin. It may be proposed that the existence of this network of adipose tissue signalling pathways, arranged in an hierarchical fashion, constitutes a metabolic repertoire which enables the organism to adapt to a range of different metabolic challenges, including starvation, reproduction, times of physical activity, stress and infection, as well as short periods of gross energy excess. However, the occurrence of more prolonged periods of energy surplus, leading to obesity, is an unusual state in evolutionary terms, and the adipose tissue signalling repertoire, although sophisticated, adapts poorly to these conditions. Rather, the responses of the adipose tissue endocrine network to obesity are maladaptive, and lay the foundations of metabolic disease.
瘦素的发现为脂肪组织研究注入了强大动力，它证明了脂肪细胞在能量调节中发挥着更为积极的作用。然而，除了瘦素之外，脂肪组织还分泌大量其他信号。细胞因子信号、肿瘤坏死因子α（TNFα）和白细胞介素 - 6（IL - 6），以及补体替代途径的成分，会影响外周燃料储存、动员和燃烧，以及能量稳态。除了对燃料代谢的急性调节外，脂肪组织还影响类固醇转化和性成熟。通过这种方式，脂肪组织是一个活跃的内分泌器官，通过局部和全身信号网络影响燃料代谢的许多方面，这些信号与已确立的脂肪组织神经内分泌调节因子相互作用。因此，胰岛素、儿茶酚胺和垂体前叶内分泌轴在多个层面上与细胞因子和瘦素相互作用。可以提出，这种以分层方式排列的脂肪组织信号通路网络的存在，构成了一种代谢指令系统，使生物体能够适应一系列不同的代谢挑战，包括饥饿、繁殖、身体活动时期、压力和感染，以及短期内的大量能量过剩。然而，从进化的角度来看，导致肥胖的更长时间的能量过剩情况是一种不寻常的状态，尽管脂肪组织信号指令系统很复杂，但对这些情况的适应性很差。相反，脂肪组织内分泌网络对肥胖的反应是适应不良的，并为代谢疾病奠定了基础。
