Uncoupling protein-2 controls adiponectin gene expression in adipose tissue through the modulation of reactive oxygen species production.
Uncoupling protein-2 (UCP2) is a mitochondrial membrane transporter expressed in white adipose tissue. We observed that circulating adiponectin levels and adiponectin gene expression in adipose tissue are reduced in UCP2-null mice. We studied whether mitochondrial activity and its control by UCP2 may regulate adiponectin gene expression. In 3T3-L1 cells, increasing UCP2 mitochondrial levels by adenoviral-mediated gene transfer induced adiponectin gene expression, whereas oligomycin and antimycin A, inhibitors of ATP synthesis and mitochondrial respiration, led to a downregulation. Reactive oxygen species (ROS) scavengers alleviated the repression of adiponectin gene expression caused by oligomycin or antimycin A. The action of ROS involves the transcription factor CHOP-10, the abundance of which was reduced in response to UCP2 and was induced by oligomycin. CHOP-10 inhibited adiponectin gene expression by interfering with the -117/-73 CCAAT/enhancer binding protein-binding region in the adiponectin gene promoter. Moreover, CHOP-10 levels were increased in adipose tissue from UCP2-null mice. Results indicate that the modulation of ROS levels by mitochondrial activity, and specifically as a consequence of the action of UCP2, controls adiponectin gene expression. This provides a physiological mechanism by which the adipose tissue energetic status may determine the extent of adiponectin release and influence systemic insulin sensitivity.
Chevillotte
Emmanuel
E
Departament de Bioquímica i Biologia Molecular. Facultat de Biologia, Universitat de Barcelona, Avda Diagonal 645, 08028 Barcelona, Spain.
Giralt
Marta
M
Miroux
Bruno
B
Ricquier
Daniel
D
Villarroya
Francesc
F
D016475:3T3 Cells; D052242:Adiponectin / Q000378:metabolism; D000273:Adipose Tissue / Q000502:physiology*; D000818:Animals; D002467:Cell Nucleus / Q000502:physiology; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051336:Mitochondrial Membranes / Q000502:physiology; D024101:Mitochondrial Proteins / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000071246:Uncoupling Protein 2
D052242:Adiponectin; D007473:Ion Channels; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C000604389:UCP2 protein, human; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2