| First Author | Blomberg R | Year | 2019 |
| Journal | Matrix Biol | Volume | 83 |
| Pages | 60-76 | PubMed ID | 31325484 |
| Mgi Jnum | J:285589 | Mgi Id | MGI:6391904 |
| Doi | 10.1016/j.matbio.2019.07.007 | Citation | Blomberg R, et al. (2019) Fibroblast activation protein restrains adipogenic differentiation and regulates matrix-mediated mTOR signaling. Matrix Biol 83:60-76 |
| abstractText | Obesity is a risk factor for multiple diseases, including diabetes, cardiovascular disease, and cancer. Within obese adipose tissue, multiple factors contribute to creating a disease-promoting environment, including metabolic dysfunction, inflammation, and fibrosis. Recent evidence points to fibrotic responses, particularly extracellular matrix remodeling, in playing a highly functional role in the pathogenesis of obesity. Fibroblast activation protein plays an essential role in remodeling collagen-rich matrices in the context of fibrosis and cancer. We observed that FAP-null mice have increased weight compared to wild-type controls, and so investigated the role of FAP in regulating diet-induced obesity. Using genetically engineered mouse models and in-vitro cell-derived matrices, we demonstrate that FAP expression by pre-adipocytes restrains adipogenic differentiation. We further show that FAP-mediated matrix remodeling alters lipid metabolism in part by regulating mTOR signaling. The impact of FAP on adipogenic differentiation and mTOR signaling together confers resistance to diet-induced obesity. The critical role of ECM remodeling in regulating obesity offers new potential targets for therapy. |
