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

Kenneth D. Chavin, Shi Qi Yang, Hui Zhi Lin, John Chatham, Vadappuram P. Chacko, Jan B. Hock, Elisabeth Walajtys-Rode, Asif Rashid, Chien Hung Chen, Chao Cheng Huang, Tzyy Choou Wu, M. Daniel Lane, Anna Mae Diehl

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5692-5700
Number of pages9
JournalJournal of Biological Chemistry
Volume274
Issue number9
DOIs
StatePublished - Feb 26 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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