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Hepatology. 2008 Oct;48(4):1087-96. doi: 10.1002/hep.22444.

Mitochondrial dysfunction contributes to the increased vulnerabilities of adiponectin knockout mice to liver injury.

Author information

1
Department of Pharmacology, Institute of Molecular Technology for Drug Discovery and Synthesis, University of Hong Kong, Hong Kong, China.

Abstract

Adiponectin is an adipocyte-derived hormone with a wide range of beneficial effects on obesity-related medical complications. Numerous epidemiological investigations in diverse ethnic groups have identified a lower adiponectin level as an independent risk factor for nonalcoholic fatty liver diseases and liver dysfunctions. Animal studies have demonstrated that replenishment of adiponectin protects against various forms of hepatic injuries, suggesting it to be a potential drug candidate for the treatment of liver diseases. This study was designed to investigate the cellular and molecular mechanisms underlying the hepatoprotective effects of adiponectin. Our results demonstrated that in adiponectin knockout (ADN-KO) mice, there was a preexisting condition of hepatic steatosis and mitochondrial dysfunction that might contribute to the increased vulnerabilities of these mice to secondary liver injuries induced by obesity and other conditions. Adenovirus-mediated replenishment of adiponectin depleted lipid accumulation, restored the oxidative activities of mitochondrial respiratory chain (MRC) complexes, and prevented the accumulation of lipid peroxidation products in ADN-KO mice but had no obvious effects on mitochondrial biogenesis. The gene and protein levels of uncoupling protein 2 (UCP2), a mitochondrial membrane transporter, were decreased in ADN-KO mice and could be significantly up-regulated by adiponectin treatment. Moreover, the effects of adiponectin on mitochondrial activities and on protection against endotoxin-induced liver injuries were significantly attenuated in UCP2 knockout mice.

CONCLUSION:

These results suggest that the hepatoprotective properties of adiponectin are mediated at least in part by an enhancement of the activities of MRC complexes through a mechanism involving UCP2.

PMID:
18698578
PMCID:
PMC2597507
DOI:
10.1002/hep.22444
[Indexed for MEDLINE]
Free PMC Article

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