ATF-2 regulates fat metabolism in Drosophila.
ATF-2 is a member of the ATF/CREB family of transcription factors that is activated by stress-activated protein kinases such as p38. To analyze the physiological role of Drosophila ATF-2 (dATF-2), we generated dATF-2 knockdown flies using RNA interference. Reduced dATF-2 in the fat body, the fly equivalent of the mammalian liver and adipose tissue, decreased survival under starvation conditions. This was due to smaller triglyceride reserves of dATF-2 knockdown flies than control flies. Among multiple genes that control triglyceride levels, expression of the Drosophila PEPCK (dPEPCK) gene was strikingly reduced in dATF-2 knockdown flies. PEPCK is a key enzyme for both gluconeogenesis and glyceroneogenesis, which is a pathway required for triglyceride synthesis via glycerol-3-phosphate. Although the blood sugar level in dATF-2 knockdown flies was almost same as that in control flies, the activity of glyceroneogenesis was reduced in the fat bodies of dATF-2 knockdown flies. Thus, reduced glyceroneogenesis may at least partly contribute to decreased triglyceride stores in the dATF-2 knockdown flies. Furthermore we showed that dATF-2 positively regulated dPEPCK gene transcription via several CRE half-sites in the PEPCK promoter. Thus, dATF-2 is critical for regulation of fat metabolism.
Okamura
Tomoo
T
Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
Shimizu
Hideyuki
H
Nagao
Tomoko
T
Ueda
Ryu
R
Ishii
Shunsuke
S
D051698:Activating Transcription Factor 2; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D048429:Cell Size; D004330:Drosophila / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004734:Energy Metabolism; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D013217:Starvation; D015996:Survival Rate; D014158:Transcription, Genetic; D014280:Triglycerides / Q000378:metabolism
C519913:ATF-2 protein, Drosophila; D051698:Activating Transcription Factor 2; D050976:Basic-Leucine Zipper Transcription Factors; D029721:Drosophila Proteins; D014280:Triglycerides; D019764:Phosphoenolpyruvate Carboxykinase (ATP)