Bradley R L, Cleveland K A, Cheatham B
Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Recent Prog Horm Res. 2001;56:329-58. doi: 10.1210/rp.56.1.329.
Obesity is a common problem in western society that is directly linked to several disease processes and is associated with significant morbidity and mortality. Adipocytes--the primary site for energy storage (as triglycerides) and release--were long suspected to have an active role in regulating body weight homeostasis and energy balance. As a result, many studies have focused on finding abnormalities in adipocyte physiology and metabolism. An ever-increasing body of evidence indicates that, in addition to serving as a repository for energy reserves, adipocytes secrete a myriad of factors that comprise a complex network of endocrine, autocrine, and paracrine signals. Very little is known regarding the molecular mechanisms utilized by the adipocyte in regulating the biosynthesis and exocytosis of these secreted products. In order to gain a better understanding of these processes, we have examined the two classical secretory pathways: regulated and constitutive. Using leptin as a model adipocyte-secretory protein, this review focuses primarily on the latter pathway. This includes regulation of leptin synthesis and secretion by insulin and glucocorticoids and, more recently, the finding that the orexigenic neuropeptide, melanin-concentrating hormone (MCH), can stimulate leptin synthesis and secretion. This chapter also incorporates new data describing the partial purification and effect of insulin on leptin-containing vesicles in rat adipocytes. These data indicate that the majority of leptin trafficking occurs via a constitutive secretory pathway and that the primary acute insulin effect on leptin secretion is to increase leptin protein content. In addition, we describe the identification and characterization of the vesicle-associated protein, pantophysin, which may play a multifunctional role in vesicle biogenesis and transport.
肥胖是西方社会的一个常见问题，它与多种疾病进程直接相关，并伴有显著的发病率和死亡率。脂肪细胞是能量储存（以甘油三酯形式）和释放的主要场所，长期以来人们一直怀疑它在调节体重稳态和能量平衡方面发挥着积极作用。因此，许多研究都集中在寻找脂肪细胞生理和代谢方面的异常。越来越多的证据表明，除了作为能量储备的储存库外，脂肪细胞还分泌大量因子，这些因子构成了一个由内分泌、自分泌和旁分泌信号组成的复杂网络。关于脂肪细胞调节这些分泌产物的生物合成和胞吐作用所利用的分子机制，我们知之甚少。为了更好地理解这些过程，我们研究了两种经典的分泌途径：调节性分泌途径和组成型分泌途径。以瘦素作为脂肪细胞分泌蛋白的模型，本综述主要关注后者。这包括胰岛素和糖皮质激素对瘦素合成和分泌的调节，以及最近发现的促食欲神经肽——黑色素浓缩激素（MCH）可以刺激瘦素的合成和分泌。本章还纳入了新的数据，描述了胰岛素对大鼠脂肪细胞中含瘦素囊泡的部分纯化和作用。这些数据表明，大多数瘦素的运输是通过组成型分泌途径进行的，胰岛素对瘦素分泌的主要急性作用是增加瘦素蛋白含量。此外，我们描述了囊泡相关蛋白泛ophysin的鉴定和特征，它可能在囊泡生物发生和运输中发挥多功能作用。
