| First Author | Paglialunga S | Year | 2015 |
| Journal | Diabetologia | Volume | 58 |
| Issue | 5 | Pages | 1071-80 |
| PubMed ID | 25754553 | Mgi Jnum | J:220847 |
| Mgi Id | MGI:5636555 | Doi | 10.1007/s00125-015-3531-x |
| Citation | Paglialunga S, et al. (2015) In adipose tissue, increased mitochondrial emission of reactive oxygen species is important for short-term high-fat diet-induced insulin resistance in mice. Diabetologia 58(5):1071-80 |
| abstractText | AIMS/HYPOTHESIS: Consuming a high-fat diet (HFD) induces insulin resistance in white adipose tissue (WAT) within 1 week. However, little is known about the initiating events. One potential mechanism that has remained largely unexplored is excessive mitochondrial emission of reactive oxygen species (ROS). METHODS: To determine the role of mitochondrial ROS emissions at the onset of insulin resistance, wild-type (WT) mice were placed on an HFD for 1 week. WAT insulin sensitivity and inflammation were assessed by western blot. In addition, we optimised/validated a method to determine ROS emissions in permeabilised WAT. RESULTS: An HFD for 1 week resulted in impaired insulin signalling, increased c-Jun NH2-terminal kinase (JNK) phosphorylation and an increase in oxidative stress. These changes were associated with an increase in fatty-acid-mediated mitochondrial ROS emissions without any change in mitochondrial respiration/content. To determine that mitochondrial ROS causes insulin resistance, we used transgenic mice that express human catalase in mitochondria (MCAT) as a model of upregulated mitochondrial antioxidant enzyme capacity. MCAT mice displayed attenuated mitochondrial ROS emission, preserved insulin signalling and no inflammatory response following an HFD. CONCLUSIONS/INTERPRETATION: Findings from this study suggest that elevated mitochondrial ROS emission contributes to HFD-induced WAT insulin resistance. |
