TY - JOUR
T1 - Mio/dChREBP coordinately increases fat mass by regulating lipid synthesis and feeding behavior in Drosophila
AU - Sassu, Eric D.
AU - McDermott, Jacqueline E.
AU - Keys, Brendan J.
AU - Esmaeili, Melody
AU - Keene, Alex C.
AU - Birnbaum, Morris J.
AU - DiAngelo, Justin R.
N1 - Funding Information:
We would like to thank the Bloomington Stock Center and the Vienna Drosophila RNAi Center for fly stocks used in this study. This study was supported by NIH Grants R21DK089391 to MJB and P20RR016464 to ACK and internal funds from Hofstra University and University of Nevada at Reno to JRD and ACK, respectively.
PY - 2012/9/14
Y1 - 2012/9/14
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bbrc.2012.08.028
DO - 10.1016/j.bbrc.2012.08.028
M3 - Article
C2 - 22910416
AN - SCOPUS:84866314172
SN - 0006-291X
VL - 426
SP - 43
EP - 48
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -