Ahima Rexford S, Qi Yong, Singhal Neel S
Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Prog Brain Res. 2006;153:155-74. doi: 10.1016/S0079-6123(06)53009-2.
Adipose tissue plays a crucial role in energy homeostasis not only in storing triglyceride, but also responding to nutrient, neural, and hormonal signals, and producing factors which control feeding, thermogenesis, immune and neuroendocrine function, and glucose and lipid metabolism. Adipose tissue secretes leptin, steroid hormones, adiponectin, inflammatory cytokines, resistin, complement factors, and vasoactive peptides. The endocrine function of adipose tissue is typified by leptin. An increase in leptin signals satiety to neuronal targets in the hypothalamus. Leptin activates Janus-activating kinase2 (Jak2) and STAT 3, resulting in stimulation of anorexigenic peptides, e.g., alpha-MSH and CART, and inhibition of orexigenic peptides, e.g., NPY and AGRP. The reduction in leptin levels during fasting stimulates appetite, decreases thermogenesis, thyroid and reproductive hormones, and increases glucocorticoids. Leptin also stimulates fatty acid oxidation, insulin release, and peripheral insulin action. These effects involve regulation of PI-3 kinase, PTP-1B, suppressor of cytokine signaling-3 (SOCS-3), and AMP-activated protein kinase in the brain and peripheral organs. There is emerging evidence that leptin, adiponectin, and resistin act through overlapping pathways. Understanding the signal transduction of adipocyte hormones will provide novel insights on the pathogenesis and treatment of obesity, diabetes, and various metabolic disorders.
脂肪组织在能量稳态中发挥着关键作用，不仅能储存甘油三酯，还能对营养、神经和激素信号作出反应，并产生控制进食、产热、免疫和神经内分泌功能以及葡萄糖和脂质代谢的因子。脂肪组织分泌瘦素、类固醇激素、脂联素、炎性细胞因子、抵抗素、补体因子和血管活性肽。脂肪组织的内分泌功能以瘦素为代表。瘦素水平升高向下丘脑的神经元靶点发出饱腹感信号。瘦素激活Janus激活激酶2（Jak2）和信号转导和转录激活因子3（STAT 3），从而刺激厌食肽，如α-黑素细胞刺激素（α-MSH）和可卡因-安非他明调节转录肽（CART），并抑制食欲肽，如神经肽Y（NPY）和刺鼠肽基因相关蛋白（AGRP）。禁食期间瘦素水平降低会刺激食欲，减少产热、甲状腺激素和生殖激素，并增加糖皮质激素。瘦素还能刺激脂肪酸氧化、胰岛素释放和外周胰岛素作用。这些作用涉及大脑和外周器官中磷脂酰肌醇-3激酶（PI-3激酶）、蛋白酪氨酸磷酸酶-1B（PTP-1B）、细胞因子信号转导抑制因子3（SOCS-3）和AMP激活的蛋白激酶的调节。越来越多的证据表明，瘦素、脂联素和抵抗素通过重叠的途径发挥作用。了解脂肪细胞激素的信号转导将为肥胖、糖尿病和各种代谢紊乱的发病机制和治疗提供新的见解。
