| First Author | Lee YS | Year | 2014 |
| Journal | Cell | Volume | 157 |
| Issue | 6 | Pages | 1339-52 |
| PubMed ID | 24906151 | Mgi Jnum | J:214449 |
| Mgi Id | MGI:5602997 | Doi | 10.1016/j.cell.2014.05.012 |
| Citation | Lee YS, et al. (2014) Increased adipocyte O2 consumption triggers HIF-1alpha, causing inflammation and insulin resistance in obesity. Cell 157(6):1339-52 |
| abstractText | Adipose tissue hypoxia and inflammation have been causally implicated in obesity-induced insulin resistance. Here, we report that, early in the course of high-fat diet (HFD) feeding and obesity, adipocyte respiration becomes uncoupled, leading to increased oxygen consumption and a state of relative adipocyte hypoxia. These events are sufficient to trigger HIF-1alpha induction, setting off the chronic adipose tissue inflammatory response characteristic of obesity. At the molecular level, these events involve saturated fatty acid stimulation of the adenine nucleotide translocase 2 (ANT2), an inner mitochondrial membrane protein, which leads to the uncoupled respiratory state. Genetic or pharmacologic inhibition of either ANT2 or HIF-1alpha can prevent or reverse these pathophysiologic events, restoring a state of insulin sensitivity and glucose tolerance. These results reveal the sequential series of events in obesity-induced inflammation and insulin resistance. |
