The role of uncoupling protein 3 in fatty acid metabolism: protection against lipotoxicity?
The role of uncoupling protein 3 in fatty acid metabolism: protection against lipotoxicity?
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DOI：
10.1079/pns2003336
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发表时间：
2004-05-01
影响因子：
7
通讯作者：
Hesselink, MKC
中科院分区：
文献类型：
--
作者：
Schrauwen, P;Hesselink, MKC
线粒体解偶联蛋白（UCP） UCP3的生理功能仍存在争议。然而，有充分的证据表明，与UCP1相反，UCP3的主要功能不是能量耗散。相反，一些证据表明UCP3与细胞脂肪酸代谢有关。在2型糖酵解肌纤维中发现了UCP3的最高表达水平，禁食和高脂肪饮食上调了UCP3。这种上调在低脂肪氧化能力的肌肉中最为明显。急性运动也能上调UCP3，而这种效应已被证明是运动引起的血浆脂肪酸水平增加的结果。相反，经常运动可以增加脂肪的氧化能力，降低UCP3的含量。基于这些数据，我们假设UCP3的功能是从线粒体基质中输出那些不能被氧化的脂肪酸，以防止脂肪酸在基质内积累。为了验证这一假设，已经进行了几项实验。阻断肉碱棕榈酰转移酶1，从而降低脂肪氧化能力，快速诱导UCP3。高脂肪饮食增加了线粒体脂肪酸的供应，也上调了UCP。然而，喂食类似数量的中链脂肪酸不会影响UCP3蛋白水平，因为中链脂肪酸可以在线粒体基质内氧化，因此不需要从基质中输出。此外，UCP3在β -氧化缺陷患者中升高，在氧化能力恢复后降低。综上所述，UCP3在促进无法氧化的脂肪酸阴离子从线粒体基质向外运输，从而保护线粒体免受脂质损伤方面具有重要的生理功能。
The physiological function of the mitochondrial uncoupling protein (UCP), UCP3, is still under debate. There is, however, ample evidence to indicate that, in contrast to UCP1, the primary function of UCP3 is not the dissipation of energy. Rather, several lines of evidence suggest that UCP3 is associated with cellular fatty acid metabolism. The highest levels of expression of UCP3 have been found in type 2 glycolytic muscle fibres, and fasting and high-fat diets up regulate UCP3. This up-regulation is most pronounced in muscle with a low fat oxidative capacity. Acute exercise also up regulates UCP3, and this effect has been shown to be a result of the exercise-induced increase in plasma fatty acid levels. In contrast, regular physical activity, which increases fat oxidative capacity, reduces UCP3 content. Based on these data it has been postulated that UCP3 functions to export those fatty acids that cannot be oxidized from the mitochondrial matrix, in order to prevent fatty acid accumulation inside the matrix. Several experiments have been conducted to test this hypothesis. Blocking carnitine palmitoyl-transferase 1, thereby reducing fat oxidative capacity, rapidly induces UCP3. High-fat diets, which increase the mitochondrial supply of fatty acids, also up regulate UCP. However, feeding a similar amount of medium-chain fatty acids, which can be oxidized inside the mitochondrial matrix and therefore do not need to be exported from the matrix, does not affect UCP3 protein levels. In addition, UCP3 is increased in patients with defective beta-oxidation and is reduced after restoring oxidative capacity. In conclusion, it is suggested that UCP3 has an important physiological function in facilitating outward transport from the mitochondrial matrix of fatty acid anions that cannot be oxidized, thereby protecting against lipid-induced mitochondrial damage.