Unger Roger H
Internal Medicine, UT Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390-8854, USA.
Biochimie. 2005 Jan;87(1):57-64. doi: 10.1016/j.biochi.2004.11.014.
In this review, we propose that actions of the lipid-lowering, apoptosis-inhibiting effects of certain "longevity genes" oppose the life-shortening consequences of lipotoxicity and lipoapoptosis. We note that lipotoxicity occurs whenever leptin action is deficient, or whenever satiety is overridden, as in forced or voluntary overfeeding ("supersizing"). The role of hyperleptinemia, we suggest, is to extend survival during famine by permitting the storage of surplus calories in adipocytes without concomitant injury to nonadipose tissues from ectopic lipid deposits. It achieves this lipid partitioning by (1) restraining the level of overnutrition so as not to exceed the available adipocyte storage space and (2) enhancing oxidation of any ectopic lipid overflow: The mechanisms of lipoapoptosis are discussed, and the possibility that metabolic syndrome is the human equivalent of rodent lipotoxicity is suggested.
在本综述中，我们提出某些“长寿基因”的降脂、抑制细胞凋亡作用可对抗脂毒性和脂肪细胞凋亡导致的寿命缩短后果。我们注意到，只要瘦素作用不足，或者只要饱腹感被打破，如在强迫或自愿过度进食（“超大分量”）时，就会发生脂毒性。我们认为，高瘦素血症的作用是通过允许多余热量在脂肪细胞中储存，而不伴随异位脂质沉积对非脂肪组织造成损伤，从而在饥荒期间延长生存期。它通过以下方式实现这种脂质分配：（1）限制营养过剩水平，以免超过可用的脂肪细胞存储空间；（2）增强任何异位脂质溢出的氧化作用。本文讨论了脂肪细胞凋亡的机制，并提出代谢综合征可能相当于人类的啮齿动物脂毒性。
