Within multicellular organisms, different cell populations can have fundamentally different metabolic needs. Cells can undergo metabolic reprogramming, a process by which metabolism is rewired to react to specific metabolic challenges or for cells to acquire novel functions. The most well-described example is the rewiring of metabolism observed in tumor cells, known as the Warburg effect. Although most intensively studied in pathological conditions, metabolic reprogramming also occurs in physiological settings, being best appreciated in the context of development. However, we still know very little about the mechanisms that implement cellular metabolic programs and regulate their reprogramming in the context of a developing tissue and their importance in organ functions.
Metabolic challenges induced by changes in the environment such as dietary nutrient scarcity, induce the coordinated adjustment of multi-organ metabolic statuses. Although animals have mechanisms for adapting feeding behavior to match nutrient intake to their current needs, a challenging task faced by them is that tissue-specific metabolic requirements need to be coordinated at the whole-organism level. However, how animals satisfy the metabolic needs of different tissues and in turn how cell-specific metabolic programs modulate animal physiology remains largely unexplored.
Female fertility has emerged as a highly relevant paradigm to study the integration of inter-organ communication with cell metabolism, and dietary nutrient availability. Oocyte production requires a high and balanced nutrient provision and the concerted action of multiple organs acting on the ovaries, modulated by the action of hormones. Because of the complex nature of the regulatory processes underlying female fertility, dissecting the molecular mechanisms which compose them requires a highly tractable experimental system such as the fruit fly. The advantage of using Drosophila at this stage is that it will allow us to approach this multidimensional network from a systems biology perspective allowing for a fast screening of molecules acting at different levels of regulation.
Using this model system, we previously have uncovered a central role for carbohydrate metabolism, namely the specific branch of pentose phosphate pathway (PPP), as a novel integration node in the regulation of animal physiology and reproduction. 1. PPP as an integrator of dietary sugars and the germline function: during early oogenesis, the germline undergoes metabolic rewiring through the upregulation of the PPP. This process is critical for oogenesis, as knockdown of PPP enzymes in the germline leads to female infertility. Consistent with the fact that the PPP is fueled by glucose, dietary sugars are also required for oocyte production. 2. PPP as a new communication axis between the ovary and the adipose tissue: upregulation of the PPP in the germline defines a new axis of communication that is required for the transcriptional regulation of a satiety factor, fit in the fat body (FB), the fly’s adipose tissue. In turn, Fit acts on the central nervous system (CNS) to regulate the appetite for sugar-rich food, which fuels PPP in the germline.
