van Dijk Gertjan, de Vries Koert, Benthem Lambertus, Nyakas Csaba, Buwalda Bauke, Scheurink Anton J W
Department of Neuroendocrinology, University of Groningen, P.O. Box 14, 9750 AA Haren, The Netherlands.
Eur J Pharmacol. 2003 Nov 7;480(1-3):31-42. doi: 10.1016/j.ejphar.2003.08.090.
Abdominal obesity is a major risk factor to attract the insulin resistance syndrome. It is proposed that abdominal obesity exposes the liver to elevated levels of free fatty acids, which activate a neuroendocrine reflex, leading to increased circulating levels of glucocorticoids. Besides directly attenuating peripheral insulin signaling, glucocorticoids oppose the activity of central nervous regulatory systems that stimulate insulin action. Among the factors that promote insulin action is leptin. Leptin regulates peripheral fuel partitioning and insulin action mainly through hypothalamic neuronal networks, which in turn, regulate endocrine activity of adipose tissue in a way comparable to thiazolidinediones. These are a class of insulin-sensitizing drugs, which exert their antidiabetic effects through the gamma isoform of peroxisome proliferator-activated receptor (PPAR-gamma). Since glucocorticoids oppose leptin action at several levels of control (including the central nervous system, CNS), it is argued that subjects easily develop obesity and associated metabolic disorders.
腹部肥胖是引发胰岛素抵抗综合征的主要危险因素。有人提出，腹部肥胖使肝脏暴露于高水平的游离脂肪酸中，这会激活一种神经内分泌反射，导致循环中糖皮质激素水平升高。糖皮质激素除了直接减弱外周胰岛素信号传导外，还会对抗刺激胰岛素作用的中枢神经调节系统的活动。促进胰岛素作用的因素之一是瘦素。瘦素主要通过下丘脑神经元网络调节外周燃料分配和胰岛素作用，而这些下丘脑神经元网络反过来又以类似于噻唑烷二酮类药物的方式调节脂肪组织的内分泌活动。噻唑烷二酮类药物是一类胰岛素增敏药物，它们通过过氧化物酶体增殖物激活受体γ（PPAR-γ）的γ亚型发挥抗糖尿病作用。由于糖皮质激素在多个控制层面（包括中枢神经系统，CNS）对抗瘦素作用，因此有人认为，这类人容易发生肥胖及相关代谢紊乱。
