Regulation of fatty acid homeostasis in cells: Novel role of leptin
Regulation of fatty acid homeostasis in cells: Novel role of leptin
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DOI：
10.1073/pnas.96.5.2327
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发表时间：
1999-03-02
影响因子：
11.1
通讯作者：
Orci, L
中科院分区：
文献类型：
--
作者：
Unger, RH;Zhou, YT;Orci, L
瘦素的一个重要功能是限制甘油三酯（TG）在脂肪细胞中的储存，同时限制TG在非脂肪细胞中的储存，从而保护它们免受脂毒性的影响。非脂肪细胞中TG含量通常保持在一个狭窄的范围内，而脂肪细胞中的TG含量则随食物摄入而变化很大，这一事实与正常非脂肪细胞中的TG稳态系统是一致的。当瘦素受体功能障碍时，非脂肪细胞如胰岛中的TG含量可增加100倍，并且组成性表达的异位高瘦素血症消耗TG，这一事实表明瘦素控制细胞内TG的稳态系统，当非脂肪细胞的TG含量高于或福尔斯低于正常范围时，它们的功能和生存能力受到损害，这一事实表明，它们的正常体内平衡受到损害。细胞内TG对于最佳功能和防止脂凋亡是关键的。到目前为止，脂毒性糖尿病的fa/fa Zucker糖尿病肥胖大鼠是唯一被证实的脂肪变性疾病，但骨骼肌和/或心肌脂毒性疾病的可能性可能需要调查，因为细胞内TG含量对自身免疫和肿瘤过程的可能影响。
It is proposed that an important function of leptin is to confine the storage of triglycerides (TG) to the adipocytes, while limiting TG storage in nonadipocytes, thus protecting them from lipotoxicity, The fact that TG content in nonadipocytes normally remains within a narrow range, while that of adipocytes varies enormously with food intake, is consistent with a system of TG homeostasis in normal nonadipocytes. The facts that when leptin receptors are dysfunctional, TG content in nonadipocytes such as islets can increase 100-fold, and that constitutively expressed ectopic hyperleptinemia depletes TG, suggest that leptin controls the homeostatic system for intracellular TG, The fact that the function and viability of nonadipocytes is compromised when their TG content rises above or falls below the normal range suggests that normal homeostasis of their intracellular TG is critical for optimal function and to prevent lipoapoptosis. Thus far, lipotoxic diabetes of fa/fa Zucker diabetic fatty rats is the only proven lipodegenerative disease, but the possibility of lipotoxic disease of skeletal and/or cardiac muscle may require investigation, as does the possible influence of the intracellular TG content on autoimmune and neoplastic processes.