The study identifies the transcription factor EB (TFEB) as a key regulator of cellular lipid metabolism during starvation. TFEB is induced by starvation through an autoregulatory feedback loop, which links the autophagic pathway to cellular energy metabolism. TFEB controls lipid metabolism via *PGC1α* and *PPARA*, and its overexpression in the liver prevents weight gain and metabolic syndrome in both diet-induced and genetic mouse models of obesity. The conservation of this mechanism in *Caenorhabditis elegans* suggests a fundamental role for TFEB in the evolution of the adaptive response to food deprivation.The study identifies the transcription factor EB (TFEB) as a key regulator of cellular lipid metabolism during starvation. TFEB is induced by starvation through an autoregulatory feedback loop, which links the autophagic pathway to cellular energy metabolism. TFEB controls lipid metabolism via *PGC1α* and *PPARA*, and its overexpression in the liver prevents weight gain and metabolic syndrome in both diet-induced and genetic mouse models of obesity. The conservation of this mechanism in *Caenorhabditis elegans* suggests a fundamental role for TFEB in the evolution of the adaptive response to food deprivation.