PgmNr D1123: The regulation of lipid storage by sex determination genes in Drosophila.

Authors:
Cezary Mikoluk 1 ; Alexis Nagengast 2 ; Justin DiAngelo 1


Institutes
1) Penn State Berks, Reading, PA; 2) Widener University, Chester, PA.


Keyword: metabolism

Abstract:

Excess nutrients are stored as triglycerides mainly in the adipose tissue of an animal. These triglycerides are located in structures called lipid droplets within adipose cells. Previous genome-wide RNAi screens in Drosophila cells identified splicing factors that play a role in lipid droplet formation. Our lab identified the SR protein, 9G8, as an important factor in fat storage as decreasing its levels results in augmented triglyceride storage in the fat body. However, whether 9G8 interacts with other proteins to affect lipid metabolism is unclear. Previous in vitro studies have implicated 9G8 in the control of doublesex (DSX) splicing by binding to transformer (TRA) and transformer2 (TRA2) to regulate sex determination; any function of these proteins in regulating metabolism is unknown. The goal of this study is to determine whether 9G8 acts with TRA, TRA2, or DSX to regulate fat storage in vivo. To test this hypothesis, we measured triglyceride and glycogen levels in flies with TRAdsRNA, TRA2dsRNA, and DSXdsRNA induced in the fat body. Decreasing TRA, TRA2 and DSX in the larval fat body has no effect on nutrient storage. However, decreasing the expression of these sex determination genes in the adult fat body resulted in an increase in triglyceride levels, a phenotype similar to the 9G8 knockdown flies. Interestingly, glycogen also accumulated when the sex determination genes were decreased in the adult fat body. To determine whether this increase in energy stores was the result of excess food consumption, we performed CAFÉ assays to measure feeding over a 24 hour period. Feeding was not increased in the TRAdsRNA, TRA2dsRNA, and DSXdsRNA flies, suggesting the triglyceride and glycogen accumulation phenotype was not the result of increased food intake. Together, these results suggest a link between mRNA splicing, sex determination and lipid metabolism and may provide insight into the mechanisms underlying tissue-specific splicing and nutrient storage in the fat body.



Flybase Genetic Index:
1. FlyBase gene symbol: x16; FBgn: FBgn0028554
2. FlyBase gene symbol: tra; FBgn: FBgn0003741
3. FlyBase gene symbol: tra2; FBgn: FBgn0003742
4. FlyBase gene symbol: dsx; FBgn: FBgn0000504