Reference - Detail
| RRC ID | 46190 |
|---|---|
| Author | Settembre C, De Cegli R, Mansueto G, Saha PK, Vetrini F, Visvikis O, Huynh T, Carissimo A, Palmer D, Klisch TJ, Wollenberg AC, Di Bernardo D, Chan L, Irazoqui JE, Ballabio A. |
| Title | TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop. |
| Journal | Nat Cell Biol |
| Abstract |
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 Ppargc1α and Ppar1α. 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. |
| Volume | 15(6) |
| Pages | 647-58 |
| Published | 2013-6-1 |
| DOI | 10.1038/ncb2718 |
| PII | ncb2718 |
| PMID | 23604321 |
| PMC | PMC3699877 |
| MeSH | Animals Autophagy / genetics Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism* Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / pharmacology Caenorhabditis elegans / metabolism Cell Line, Tumor Energy Metabolism Feedback, Physiological Gene Expression Regulation HeLa Cells Homeostasis Humans Lipid Metabolism* Liver / metabolism Lysosomes / genetics Male Metabolic Syndrome / genetics Metabolic Syndrome / metabolism* Metabolic Syndrome / prevention & control Mice Mice, Inbred C57BL Mice, Transgenic Obesity / genetics Obesity / metabolism* PPAR alpha / metabolism Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Starvation / genetics Starvation / metabolism* Trans-Activators / metabolism Transcription Factors Transcription, Genetic Weight Gain |
| IF | 20.042 |
| Times Cited | 391 |
| WOS Category | CELL BIOLOGY |
| Resource | |
| C.elegans | tm1978 |