| First Author | Sun K | Year | 2014 |
| Journal | Nat Commun | Volume | 5 |
| Pages | 3485 | PubMed ID | 24647224 |
| Mgi Jnum | J:210307 | Mgi Id | MGI:5570447 |
| Doi | 10.1038/ncomms4485 | Citation | Sun K, et al. (2014) Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction. Nat Commun 5:3485 |
| abstractText | We recently identified endotrophin as an adipokine with potent tumour-promoting effects. However, the direct effects of local accumulation of endotrophin in adipose tissue have not yet been studied. Here we use a doxycycline-inducible adipocyte-specific endotrophin overexpression model to demonstrate that endotrophin plays a pivotal role in shaping a metabolically unfavourable microenvironment in adipose tissue during consumption of a high-fat diet (HFD). Endotrophin serves as a powerful co-stimulator of pathologically relevant pathways within the 'unhealthy' adipose tissue milieu, triggering fibrosis and inflammation and ultimately leading to enhanced insulin resistance. We further demonstrate that blocking endotrophin with a neutralizing antibody ameliorates metabolically adverse effects and effectively reverses metabolic dysfunction induced during HFD exposure. Collectively, our findings demonstrate that endotrophin exerts a major influence in adipose tissue, eventually resulting in systemic elevation of pro-inflammatory cytokines and insulin resistance, and the results establish endotrophin as a potential target in the context of metabolism and cancer. |
