Leptin: fundamental aspects
Leptin: fundamental aspects
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DOI：
10.1038/sj.ijo.0800791
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发表时间：
1999-02-01
影响因子：
4.9
通讯作者：
Rayner, DV
中科院分区：
文献类型：
--
作者：
Trayhurn, P;Hoggard, N;Rayner, DV
ob 基因的产物瘦素的发现使人们对能量平衡调节的理解取得了重大进展。现在人们认识到瘦素在白色脂肪组织之外的几个器官中产生，包括棕色脂肪、胎盘和胎儿组织（例如心脏和骨/软骨）。该激素具有多种功能——抑制食物摄入、刺激/维持能量消耗、作为生殖系统的信号以及作为影响一系列过程（例如胰岛素分泌、脂肪分解、糖运输）的“代谢”激素。白色脂肪产生瘦素会受到多种调节因素的影响，包括胰岛素和糖皮质激素（具有刺激性），以及禁食和 B 型肾上腺素受体激动剂（具有抑制性）。交感神经系统通过 BB 肾上腺素受体发挥作用，在白色脂肪调节瘦素产生中发挥关键作用。瘦素受体基因广泛表达，几种剪接变体表现出不同的表达模式。长型变体 (Ob-Rb) 尤其在下丘脑中表达，尽管它在其他组织中的发现也越来越多。瘦素通过多种神经内分泌系统发挥其核心作用，包括神经肽 Y、胰高血糖素样肽-1、黑皮质素、促肾上腺皮质激素释放激素 (CRH) 以及可卡因和安非他明调节转录物 (CART)。从本质上讲，瘦素系统现在显得非常复杂，这种激素以远远超越最初的脂肪抑制概念的方式参与一系列生理过程。这种复杂性可能会降低瘦素系统作为抗肥胖治疗靶点的潜力。
The discovery of leptin, the product of the ob gene, has led to major developments in understanding the regulation of energy balance. It is now recognised that leptin is produced in several organs additional to white adipose tissue, including brown fat, the placenta and fetal tissues (such as heart and bone/cartilage). The hormone has multiple functions-in inhibiting food intake, in the stimulation/maintenance of energy expenditure, as a signal to the reproductive system and as a 'metabolic' hormone influencing a range of processes (for example, insulin secretion, lipolysis, sugar transport). The production of leptin by white fat is subject to a number of regulatory influences, including insulin and glucocorticoids (which are stimulatory), and fasting and B-adrenoceptor agonists (which are inhibitory). A key role in the regulation of leptin production by white fat is envisaged for the sympathetic system, operating through BB-adrenoceptors. The leptin receptor gene is widely expressed, with the several splice variants exhibiting different patterns of expression. The long form variant (Ob-Rb) is expressed particularly in the hypothalamus, although it is being increasingly identified in other tissues. Leptin exerts its central effects through several neuroendocrine systems, including neuropeptide Y, glucagon-like peptide-1, melanocortins, corticotrophin releasing hormone (CRH) and cocaine- and amphetamine-regulated transcript (CART). In essence, the leptin system now appears highly complex, the hormone being involved in a range of physiological processes in a manner far transcending the initial lipostatic concept. This complexity may reduce the potential of the leptin system as a target for anti-obesity therapy.