Journal
INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
Volume 43, Issue 9, Pages 829-838Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.ibmb.2013.06.007
Keywords
FoxO; 20-Hydroxyecdysone; Brummer; Acid lipase-1; Lipolysis; Fat body
Categories
Funding
- 973 program [2012CB114605]
- Natural Science Foundation of China [31101670, 31125025]
- Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences [2011KIP303]
- Shanghai Municipal Education Commission [10JC1416700, 12XD1406900]
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In a previous study, we have shown that the molting hormone, 20-hydroxyecdysone (20E), reduces insect food consumption resulting in fat body lipolysis during the non-feeding molting and pupation stages, and assumed that the transcription factor FoxO is involved in this process. To verify this hypothesis, we cloned foxO from the silkworm, Bombyx mori. During molting and pupation, FoxO is highly expressed and predominantly localizes in the nuclei of fat body cells. 20E induced foxO mRNA expression and FoxO nuclear localization resulting in an increase of FoxO transcriptional activity. RNAi of foxO prior to the 4th larval molting downregulated two lipase genes - the insect adipose triacylglycerol lipase homologue, brummer, and an acid lipase, acid lipase-1, in the fat body. Overexpression of the constitutively-active form of foxO (foxO(CA)) upregulated brummer and acid lipase-1 in both the fat body and Bombyx Bm-12 cells. Putative FoxO-response elements (FREs) are present in the promoter regions of brummer and acid lipase-1, and mutation of the FREs attenuated their FoxO-induced luciferase activities. ChIP assay revealed that FoxO binds directly to those FREs. Moreover, foxO(CA) overexpression in vivo doubled lipid concentration in the hemolymph, increased total lipase activity, and slightly but significantly reduced lipid content in the fat body. Taken together, we conclude that 20E increases the transcriptional activity of FoxO which, in turn, upregulates brummer and acid lipase-1 and induces lipolysis in the Bombyx fat body during molting and pupation. (c) 2013 Elsevier Ltd. All rights reserved.
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