Obesity induces expression of uncoupling protein-2 in hepatocytes and promotes liver ATP depletion
Obesity induces expression of uncoupling protein-2 in hepatocytes and promotes liver ATP depletion
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DOI：
10.1074/jbc.274.9.5692
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发表时间：
1999-02-26
影响因子：
4.8
通讯作者：
Diehl, AM
中科院分区：
文献类型：
--
作者：
Chavin, KD;Yang, SQ;Diehl, AM
解偶联蛋白2(UCP2)使呼吸从氧化磷酸化中解离，并可能通过影响能量代谢而导致肥胖。由于肥胖患者的基础代谢率降低，UCP2的表达预计也会减少。矛盾的是，遗传性肥胖(ob/ob)小鼠肝脏中UCP2的mRNA表达增加，原位杂交和免疫组织化学分析表明，肥胖小鼠肝细胞中UCP2的mRNA和蛋白表达增加，而瘦小鼠肝细胞中不表达UCP2。从ob/ob肝脏分离的线粒体表现出H+漏出率的增加，当电子传递速率被抑制时，H+漏出率部分地消散了线粒体膜电位。此外，肝脏的ATP储存量减少，这些肝脏在短暂性肝缺血后更容易发生坏死。因此，肝细胞通过上调UCP2来适应肥胖。然而，由于这降低了能量捕获的效率，当能量需求急剧增加时，细胞容易受到ATP耗尽的影响。
Uncoupling protein 2 (UCP2) uncouples respiration from oxidative phosphorylation and may contribute to obesity through effects on energy metabolism. Because basal metabolic rate is decreased in obesity, UCP2 expression is predicted to be reduced. Paradoxically, hepatic expression of UCP2 mRNA is increased in genetically obese (ob/ob) mice, In situ hybridization and immunohistochemical analysis of ob/ob livers demonstrate that UCP2 mRNA and protein expression are increased in hepatocytes, which do not express UCP2 in lean mice. Mitochondria isolated from ob/ob livers exhibit an increased rate of H+ leak which partially dissipates the mitochondrial membrane potential when the rate of electron transport is suppressed. In addition, hepatic ATP stores are reduced and these livers are more vulnerable to necrosis after transient hepatic ischemia. Hence, hepatocytes adapt to obesity by up-regulating UCP2. However, because this decreases the efficiency of energy trapping, the cells become vulnerable to ATP depletion when energy needs increase acutely.