During development, animals usually undergo a rapid growth phase before reaching a homeostatic state. The increase in cell size and number during the growth phase requires a large amount of lipids; while in the static state, excess lipids are usually stored in preparation for nutrient-limited conditions. How cells coordinate growth and fat storage is not fully understood.

 

By screening for genes that affect lipid storage in the fruitfly Drosophila, Dr. Xun Huang and his colleagues at the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, identified CDP-diacylglycerol synthetase, CdsA as an important gate-keeper in balancing fat storage and cell growth. CdsA mutation leads to significant accumulation of neutral lipids in many tissues along with reduced cell/organ size. These phenotypes can be traced back to a reduction in the level of PI and subsequent low activity of the insulin pathway. Overexpressing CdsA rescues the fat storage and cell growth phenotypes of insulin pathway mutants, suggesting that there is positive feedback regulation between the insulin pathway and CdsA in coordinating rapid cell/tissue growth and fat storage. CdsA regulates the level of PI, which modulates insulin pathway activity; insulin pathway activity, in turn, influences the level of CdsA. Besides the positive feedback regulation, they also revealed that phosphatidylinositol (PI) from a cell non-autonomous origin and a diacylglycerol (DAG)-to-phosphatidylethanolamine (PE) route mediated by the choline/ethanolamine phosphotransferase Bbc ensure the growth of fat cells in CdsA RNAi larvae.

 

This work has been published online on PLoS Genetics with Yuan Li as the first author and Dr. Guanghou Shui as co-corresponding author. This research was supported by grants from Ministry of Science and Technology of China and National Natural Science Foundation of China.

 

AUTHOR CONTACT:

Xun Huang, Ph.D.

Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.

E-mail: xhuang@genetics.ac.cn

 

 

 

 

Figure: CdsA acts at the branch of PA metabolism and is positively feedback regulated by insulin pathway.