Mio/dChREBP coordinately increases fat mass by regulating lipid synthesis and feeding behavior in Drosophila

Eric D. Sassu, Jacqueline E. McDermott, Brendan J. Keys, Melody Esmaeili, Alex C. Keene, Morris J. Birnbaum, Justin R. DiAngelo

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)43-48
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume426
Issue number1
DOIs
StatePublished - Sep 14 2012

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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