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.