| First Author | Settembre C | Year | 2013 |
| Journal | Nat Cell Biol | Volume | 15 |
| Issue | 6 | Pages | 647-58 |
| PubMed ID | 23604321 | Mgi Jnum | J:198501 |
| Mgi Id | MGI:5496946 | Doi | 10.1038/ncb2718 |
| Citation | Settembre C, et al. (2013) TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop. Nat Cell Biol 15(6):647-58 |
| abstractText | The lysosomal-autophagic pathway is activated by starvation and plays an important role in both cellular clearance and lipid catabolism. However, the transcriptional regulation of this pathway in response to metabolic cues is uncharacterized. Here we show that the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, is induced by starvation through an autoregulatory feedback loop and exerts a global transcriptional control on lipid catabolism via Ppargc1alpha and Ppar1alpha. Thus, during starvation a transcriptional mechanism links the autophagic pathway to cellular energy metabolism. The conservation of this mechanism in Caenorhabditis elegans suggests a fundamental role for TFEB in the evolution of the adaptive response to food deprivation. Viral delivery of TFEB to the liver prevented weight gain and metabolic syndrome in both diet-induced and genetic mouse models of obesity, suggesting a new therapeutic strategy for disorders of lipid metabolism. |
