TY - JOUR TI - E2F/Dp inactivation in fat body cells triggers systemic metabolic changes AU - Zappia, Maria Paula AU - Guarner, Ana AU - Kellie-Smith, Nadia AU - Rogers, Alice AU - Morris, Robert AU - Nicolay, Brandon AU - Boukhali, Myriam AU - Haas, Wilhelm AU - Dyson, Nicholas J AU - Frolov, Maxim V A2 - Bellen, Hugo J A2 - VijayRaghavan, K A2 - Edgar, Bruce A VL - 10 PY - 2021 DA - 2021/07/12 SP - e67753 C1 - eLife 2021;10:e67753 DO - 10.7554/eLife.67753 UR - https://doi.org/10.7554/eLife.67753 AB - The E2F transcription factors play a critical role in controlling cell fate. In Drosophila, the inactivation of E2F in either muscle or fat body results in lethality, suggesting an essential function for E2F in these tissues. However, the cellular and organismal consequences of inactivating E2F in these tissues are not fully understood. Here, we show that the E2F loss exerts both tissue-intrinsic and systemic effects. The proteomic profiling of E2F-deficient muscle and fat body revealed that E2F regulates carbohydrate metabolism, a conclusion further supported by metabolomic profiling. Intriguingly, animals with E2F-deficient fat body had a lower level of circulating trehalose and reduced storage of fat. Strikingly, a sugar supplement was sufficient to restore both trehalose and fat levels, and subsequently rescued animal lethality. Collectively, our data highlight the unexpected complexity of E2F mutant phenotype, which is a result of combining both tissue-specific and systemic changes that contribute to animal development. KW - e2f/rb pathway KW - sugar metabolism KW - trehalose KW - triglycerides KW - proteome JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -