Mio/dChREBP coordinately increases fat mass by regulating lipid synthesis and feeding behavior in Drosophila.
During nutrient excess, triglycerides are synthesized and stored to provide energy during times of famine. The presence of high glucose leads to the activation of carbohydrate response element binding protein (ChREBP), a transcription factor that induces the expression of a number of glycolytic and lipogenic enzymes. ChREBP is expressed in major metabolic tissues and while we have a basic understanding of ChREBP function in liver, in vivo genetic systems to study the function of ChREBP in other tissues are lacking. In this study, we characterized the role of the Drosophila homolog of ChREBP, Mlx interactor (Mio), in controlling fat accumulation in larvae and adult flies. In Mio mutants, high sugar-induced lipogenic enzyme mRNA expression is blunted and lowering Mio levels specifically in the fat body using RNA interference leads to a lean phenotype. A lean phenotype is also observed when the gene bigmax, the fly homolog of ChREBP's binding partner Mlx, is decreased in the larval fat body. Interestingly, depleting Mio in the fat body results in decreased feeding providing a potential cause of the lowered triglycerides observed in these animals. However, Mio does not seem to function as a general regulator of hunger-induced behaviors as decreasing fat body Mio levels has no effect on sleep under fed or starved conditions. Together, these data implicate a role for Mio in controlling fat accumulation in Drosophila and suggests that it may act as a nutrient sensor in the fat body to coordinate feeding behavior with nutrient availability.
Department of Biology, Hofstra University, Hempstead, NY 11549, USA.
Eric D
ED
Sassu
Jacqueline E
JE
McDermott
Brendan J
BJ
Keys
Melody
M
Esmaeili
Alex C
AC
Keene
Morris J
MJ
Birnbaum
Justin R
JR
DiAngelo
D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005216:Fat Body / Q000378:metabolism / Q000502:physiology*; D005223:Fats / Q000378:metabolism*; D005247:Feeding Behavior; D050155:Lipogenesis / Q000235:genetics / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D020218:Response Elements; D014280:Triglycerides / Q000096:biosynthesis / Q000378:metabolism*
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D005223:Fats; D009687:Nuclear Proteins; D014280:Triglycerides; C581832:bigmax protein, Drosophila; C484002:mio protein, Drosophila