Unger R H, Zhou Y T, Orci L
Gifford Laboratories, Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2327-32. doi: 10.1073/pnas.96.5.2327.
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.
有人提出，瘦素的一个重要功能是将甘油三酯（TG）的储存限制在脂肪细胞内，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。非脂肪细胞中的TG含量通常保持在狭窄范围内，而脂肪细胞中的TG含量则随食物摄入量大幅变化，这一事实与正常非脂肪细胞中TG的稳态系统一致。当瘦素受体功能失调时，胰岛等非脂肪细胞中的TG含量可增加100倍，而组成性表达的异位高瘦素血症会消耗TG，这些事实表明瘦素控制着细胞内TG的稳态系统。当非脂肪细胞的TG含量高于或低于正常范围时，其功能和活力会受到损害，这一事实表明细胞内TG的正常稳态对于最佳功能和预防脂肪凋亡至关重要。到目前为止，fa/fa Zucker糖尿病脂肪大鼠的脂毒性糖尿病是唯一已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研究，细胞内TG含量对自身免疫和肿瘤过程的可能影响也需要研究。
