| First Author | Chevillotte E | Year | 2007 |
| Journal | Diabetes | Volume | 56 |
| Issue | 4 | Pages | 1042-50 |
| PubMed ID | 17395745 | Mgi Jnum | J:122094 |
| Mgi Id | MGI:3713163 | Doi | 10.2337/db06-1300 |
| Citation | Chevillotte E, et al. (2007) Uncoupling protein-2 controls adiponectin gene expression in adipose tissue through the modulation of reactive oxygen species production. Diabetes 56(4):1042-50 |
| abstractText | 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. |
