ATF-2 Regulates Fat Metabolism inDrosophila

Abstract

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.

Glucosylceramide synthase in the fat body controls energy metabolism in Drosophila

“…A recent study has shown that p38-ATF2 signaling leads to the accumulation of stored energy in Drosophila ( 17 ). In the present study, we showed that dGlcT-1 activates p38-ATF2 signaling.…”

“…3B ) ( 17 ). Increased FAS and decreased PEPCK mRNA expression phenotypes observed in dGlcT-1 knockdown fl ies were similar to that in dATF2 knockdown fl ies.…”

“…Overexpression of dATF2 increases TAG levels, whereas dATF2 knockdown decreases TAG levels ( 17 ). Thus, we also examined whether dGlcT-1 expression affects dATF2-mediated effects on stored TAG levels by staining fat bodies with lipophilic dyes.…”

Longevity and stress resistance are affected by activation of TOR/Myc in progenitor cells of Drosophila gut

“…A possible reason why insulin and AKH regulatory signals increased simultaneously could be that transgenic flies have a faster metabolism or that these outputs are regulated by peptide synthesis or release. Drosophila PEPCK is involved in gluconeogenesis and glycerogenesis [46]. Interestingly, elevated pepck levels correspond with elevated whole body glucose levels in Rheb and Myc-Rheb expressing flies.…”

Seasonal shifts in accumulation of glycerol biosynthetic gene transcripts in mountain pine beetle, Dendroctonus ponderosae Hopkins (Coleoptera: Curculionidae), larvae

“…13 Reshef, 2003). Shown previously to be important in fat metabolism in other insects (Okamura et al, 2007), glyceroneogenesis, like gluconeogenesis, is highly regulated by the transcript accumulation of PEPCK. Fold-change increases for PEPCK mRNA in mountain pine beetle larvae during periods of cold exposure were far greater than any other gene investigated within this study, reaching a high of 58.64-fold 18 March.…”