Cabut Coordinates Metabolism and Clock in Response to Nutrient Sensing

Using a Drosophila fruit fly model to study sugar sensing, researchers have discovered that the transcription factor and developmental growth regulator, cabut, coordinates energy metabolism as well as the circadian clock in response to sugar sensing.

Sugar feeding in flies leads to a sugar-sensing pathway that along one branch induces expression of specific genes, but also triggers a repression branch of the sugar-sensing transcriptional network via cabut (CBT, encoded by cbt) in Drosophila melanogaster. However, mechanisms of transcriptional repression upon sugar sensing have remained elusive. In the new collaborative study of response to sugar, a team of researchers, led by Prof. Ville Hietakangas of the University of Helsinki (Helsinki, Finland) and Prof. Sebastian Kadener of the Hebrew University of Jerusalem (Jerusalem, Israel), found that induction of cbt represses accumulation of several metabolic targets and provides a regulatory link between nutrient sensing and the circadian clock.

Among the metabolic targets, CBT was found to repress the expression of both isoforms of the enzyme phosphoenolpyruvate carboxykinase (PEPCK). They also found that upon sugar feeding cbt is rapidly induced through direct regulation by the Mondo‐Mlx transcription factor complex. Deregulation of pepck1 in mlx mutants was found to underly the imbalance of glycerol and glucose metabolism as well as the developmental lethality of these mutants.

In addition to a subset of metabolic genes per se, the researchers found that CBT also targets a subset of genes regulated by the circadian clock and represses the cycling of metabolic target genes of this clock. They observed that perturbation of CBT levels even led to deregulation of the circadian transcriptome and circadian behavioral patterns.

The study, by Bartok O, Mari Teesalu, et al, was published online April 27, 2015, in EMBO Journal.

Related Links:
University of Helsinki
Hebrew University of Jerusalem