Obesity induces expression of uncoupling protein-2 in hepatocytes and promotes liver ATP depletion

被引:372
作者
Chavin, KD
Yang, SQ
Lin, HZ
Chatham, J
Chacko, VP
Hoek, JB
Walajtys-Rode, E
Rashid, A
Chen, CH
Huang, CC
Wu, TC
Lane, MD
Diehl, AM
机构
[1] Johns Hopkins Univ, Dept Med, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Dept Surg, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Dept Radiol, Baltimore, MD 21205 USA
[4] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21205 USA
[5] Johns Hopkins Univ, Dept Biol Chem, Baltimore, MD 21205 USA
[6] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA
关键词
D O I
10.1074/jbc.274.9.5692
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:5692 / 5700
页数:9
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