| First Author | Stallings NR | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 8 | Pages | e71793 |
| PubMed ID | 23967244 | Mgi Jnum | J:206353 |
| Mgi Id | MGI:5550055 | Doi | 10.1371/journal.pone.0071793 |
| Citation | Stallings NR, et al. (2013) TDP-43, an ALS linked protein, regulates fat deposition and glucose homeostasis. PLoS One 8(8):e71793 |
| abstractText | The identification of proteins which determine fat and lean body mass composition is critical to better understanding and treating human obesity. TDP-43 is a well-conserved RNA-binding protein known to regulate alternative splicing and recently implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). While TDP-43 knockout mice show early embryonic lethality, post-natal conditional knockout mice show weight loss, fat depletion, and rapid death, suggesting an important role for TDP-43 in regulating energy metabolism. Here we report, that over-expression of TDP-43 in transgenic mice can result in a phenotype characterized by increased fat deposition and adipocyte hypertrophy. In addition, TDP-43 over-expression in skeletal muscle results in increased steady state levels of Tbc1d1, a RAB-GTPase activating protein involved in Glucose 4 transporter (Glut4) translocation. Skeletal muscle fibers isolated from TDP-43 transgenic mice show altered Glut4 translocation in response to insulin and impaired insulin mediated glucose uptake. These results indicate that levels of TDP-43 regulate body fat composition and glucose homeostasis in vivo. |
