title: Upregulation of UCP2 by adiponectin: the involvement of mitochondrial superoxide and hnRNP K.
abstract: BACKGROUND
  The adipocyte-derived hormone adiponectin elicits protective functions against fatty liver diseases and hepatic injuries at least in part by stimulating the expression of a mitochondrial inner membrane transporter, uncoupling protein 2 (UCP2). The present study was designed to investigate the cellular and molecular mechanisms underlying adiponectin-induced UCP2 expression.
  
  
  RESULTS
  Mice were treated with adiponectin and/or different drug inhibitors. Parenchymal (PCs) and nonparenchymal (NPCs) cells were fractionated from the liver tissues for mitochondria isolation, Western blotting and quantitative PCR analysis. Mitochondrial superoxide production was monitored by MitoSOX staining and flow cytometry analysis. Compared to control mice, the expression of UCP2 was significantly lower in NPCs, but not PCs of adiponectin knockout mice (AKO). Both chronic and acute treatment with adiponectin selectively increased the mRNA and protein abundance of UCP2 in NPCs, especially in the enriched endothelial cell fractions. The transcription inhibitor actinomycin D could not block adiponectin-induced UCP2 expression, whereas the protein synthesis inhibitor cycloheximide inhibited the elevation of UCP2 protein but not its mRNA levels. Mitochondrial content of heterogeneous nuclear ribonucleoprotein K (hnRNP K), a nucleic acid binding protein involved in regulating mRNA transportation and stabilization, was significantly enhanced by adiponectin, which also evoked a transient elevation of mitochondrial superoxide. Rotenone, an inhibitor of mitochondrial respiratory complex I, abolished adiponectin-induced superoxide production, hnRNP K recruitment and UCP2 expression.
  
  
  CONCLUSIONS
  Mitochondrial superoxide production stimulated by adiponectin serves as a trigger to initiate the translocation of hnRNP K, which in turn promotes UCP2 expressions in liver.
authors.affiliation: Department of Pharmacology and Pharmacy, University of Hong Kong, Hong Kong, China.
authors.forename: Mingyan
authors.initials: M
authors.lastname: Zhou
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
authors.forename: Paul K H
authors.initials: PK
authors.lastname: Tam
authors.forename: Karen S L
authors.initials: KS
authors.lastname: Lam
authors.forename: Bosheng
authors.initials: B
authors.lastname: Huang
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Lee
authors.forename: Donghai
authors.initials: D
authors.lastname: Wu
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
mesh_terms: D052242:Adiponectin / Q000502:physiology*; D000818:Animals; D042783:Endothelial Cells / Q000378:metabolism; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000378:metabolism*; D007473:Ion Channels / Q000096:biosynthesis*; D008099:Liver / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D008930:Mitochondria, Liver / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis; D013481:Superoxides / Q000378:metabolism*; D000071246:Uncoupling Protein 2; D015854:Up-Regulation
chemical_list: D052242:Adiponectin; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D007473:Ion Channels; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D013481:Superoxides