Mitochondrial uncoupling and lipid metabolism in adipocytes
Mitochondrial uncoupling and lipid metabolism in adipocytes
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DOI：
10.1042/bst0290791
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发表时间：
2001-01-01
影响因子：
3.9
通讯作者：
Brauner, P
中科院分区：
文献类型：
--
作者：
Kopecky, J;Rossmeisl, M;Brauner, P
白色脂肪组织的代谢参与体脂含量的控制。体外实验表明，依赖线粒体ATP的生产，以及激素对代谢和能量的脂肪细胞的影响之间的相互联系的脂肪生成。因此，脂肪细胞中线粒体解偶联导致能量耗散的刺激和ATP合成的抑制可能有助于控制脂质代谢和肥胖。这得到了脂肪细胞中质子转运蛋白（例如解偶联蛋白（UCP）2和5）和一些阴离子转运蛋白的表达以及通过减少肥胖的药物治疗诱导白色脂肪中UCP 1和UCP 3的支持。脂肪细胞中UCPs的表达与白色脂肪的积累呈负相关，在aP 2-Ucp 1转基因小鼠中脂肪特异性启动子UCP 1的表达减轻了遗传或饮食因素诱导的肥胖。肥胖抵抗，伴随着脂肪细胞线粒体解偶联和能量消耗增加，是由于UCP 1在白色脂肪中的异位表达，而不是在棕色脂肪中。可能由于转基因小鼠白色脂肪中ATP/ADP比值降低，脂肪细胞中脂肪酸合成和去甲肾上腺素的脂解作用均相对较低。这些结果支持脂肪细胞中的质子转运蛋白在控制肥胖中的作用。这些蛋白质在白色脂肪中的主要功能可能是调节脂肪生成和细胞内激素信号传导。根据白色脂肪细胞的低氧化能力，能量消耗的增加可能相对不重要。
Metabolism of white adipose tissue is involved in the control of body fat content. In vitro experiments indicated a dependence of lipogenesis on mitochondrial ATP production, as well as a reciprocal link between hormonal effects on metabolism and energetics of adipocytes. Therefore, mitochondrial uncoupling in adipocytes that results in stimulation of energy dissipation and depression of ATP synthesis may contribute to control of lipid metabolism and adiposity. This is supported by the expression of protonophoric proteins in adipocytes, e.g. uncoupling proteins (UCPs) 2 and 5, and some anion transporters, and induction of UCP1 and UCP3 in white fat by pharmacological treatments that reduce adiposity. Negative correlation between expression of UCPs in adipocytes and accumulation of white fat was also found. Expression of UCP1 from the adipose-specific promoter in aP2-Ucp1 transgenic mice mitigated obesity induced by genetic or dietary factors. The obesity resistance, accompanied by mitochondrial uncoupling in adipocytes and increased energy expenditure, resulted from ectopic expression of UCP1 in white but not in brown fat. Probably due to depression of ATP/ADP ratio in white fat of transgenic mice, both fatty acid synthesis and lipolytic action of noradrenaline in adipocytes were relatively low. These results support the role of protonophoric proteins in adipocytes in the control of adiposity. The main function of these proteins in white fat may be modulation of lipogenesis and intracellular hormone signalling. Augmentation of energy expenditure may be of relatively small importance, in accordance with the low oxidative capacity of white adipocytes.