Germline proliferation trades off with lipid metabolism in Drosophila.

Little is known about the metabolic basis of life-history trade-offs but lipid stores seem to play a pivotal role. During reproduction, an energetically highly costly process, animals mobilize fat reserves. Conversely, reduced or curtailed reproduction promotes lipid storage in many animals. Systemic signals from the gonad seem to be involved: Caenorhabditis elegans lacking germline stem cells display endocrine changes, have increased fat stores and are long-lived. Similarly, germline-ablated Drosophila melanogaster exhibit major somatic physiological changes, but whether and how germline loss affects lipid metabolism remains largely unclear. Here we show that germline-ablated flies have profoundly altered energy metabolism at the transcriptional level and store excess fat as compared to fertile flies. Germline activity thus constrains or represses fat accumulation, and this effect is conserved between flies and worms. More broadly, our findings confirm that lipids represent a major energetic currency in which costs of reproduction are paid.

Transcriptomic evidence for a trade-off between germline proliferation and immunity in Drosophila.

Life-history theory posits that investment into reproduction might occur at the expense of investment into somatic maintenance, including immune function. If so, reduced or curtailed reproductive effort might be expected to increase immunity. In support of this notion, work in Caenorhabditis elegans has shown that worms lacking a germline exhibit improved immunity, but whether the antagonistic relation between germline proliferation and immunity also holds for other organisms is less well understood. Here, we report that transgenic ablation of germ cells in late development or early adulthood in Drosophila melanogaster causes elevated baseline expression and increased induction of Toll and Imd immune genes upon bacterial infection, as compared to fertile flies with an intact germline. We also identify immune genes whose expression after infection differs between fertile and germline-less flies in a manner that is conditional on their mating status. We conclude that germline activity strongly impedes the expression and inducibility of immune genes and that this physiological trade-off might be evolutionarily conserved.

Amino acid modulation of lifespan and reproduction in Drosophila.

Manipulating amino acid (AA) intake in Drosophila can profoundly affect lifespan and reproduction. Remarkably, AA manipulation can uncouple the commonly observed trade-off between these traits. This finding seems to challenge the idea that this trade-off is due to competitive resource allocation, but here we argue that this view might be too simplistic. We also discuss the mechanisms of the AA response, mediated by the IIS/TOR and GCN2 pathways. Elucidating how these pathways respond to specific AA will likely yield important insights into how AA modulate the reproduction-lifespan relationship. The Drosophila model offers powerful genetic tools, combined with options for precise diet manipulation, to address these fundamental questions.

Endocrine uncoupling of the trade-off between reproduction and somatic maintenance in eusocial insects.

In most animals reproduction trades off with somatic maintenance and survival. Physiologically this trade-off is mediated by hormones with opposite effects on reproduction and maintenance. In many insects, this regulation is achieved by an endocrine network that integrates insulin-like/IGF-1 signaling (IIS), juvenile hormone (JH), and the yolk precursor vitellogenin (Vg) (or, more generally, yolk proteins [YPs]). Downregulation of this network promotes maintenance and survival at the expense of reproduction. Remarkably, however, queens of highly eusocial social insects exhibit both enormous reproductive output and longevity, thus escaping the trade-off. Here we argue - based on recent evidence - that the proximate reason for why eusocial insects can decouple this trade-off is that they have evolved a different 'wiring' of the IIS-JH-Vg/YP circuit.

Drosophila melanogaster larvae make nutritional choices that minimize developmental time.

Organisms from slime moulds to humans carefully regulate their macronutrient intake to optimize a wide range of life history characters including survival, stress resistance, and reproductive success. However, life history characters often differ in their response to nutrition, forcing organisms to make foraging decisions while balancing the trade-offs between these effects. To date, we have a limited understanding of how the nutritional environment shapes the relationship between life history characters and foraging decisions. To gain insight into the problem, we used a geometric framework for nutrition to assess how the protein and carbohydrate content of the larval diet affected key life history traits in the fruit fly, Drosophila melanogaster. In no-choice assays, survival from egg to pupae, female and male body size, and ovariole number - a proxy for female fecundity - were maximized at the highest protein to carbohydrate (P:C) ratio (1.5:1). In contrast, development time was minimized at intermediate P:C ratios, around 1:2. Next, we subjected larvae to two-choice tests to determine how they regulated their protein and carbohydrate intake in relation to these life history traits. Our results show that larvae targeted their consumption to P:C ratios that minimized development time. Finally, we examined whether adult females also chose to lay their eggs in the P:C ratios that minimized developmental time. Using a three-choice assay, we found that adult females preferentially laid their eggs in food P:C ratios that were suboptimal for all larval life history traits. Our results demonstrate that D. melanogaster larvae make foraging decisions that trade-off developmental time with body size, ovariole number, and survival. In addition, adult females make oviposition decisions that do not appear to benefit the larvae. We propose that these decisions may reflect the living nature of the larval nutritional environment in rotting fruit. These studies illustrate the interaction between the nutritional environment, life history traits, and foraging choices in D. melanogaster, and lend insight into the ecology of their foraging decisions.

Nutritional control of body size through FoxO-Ultraspiracle mediated ecdysone biosynthesis.

Despite their fundamental importance for body size regulation, the mechanisms that stop growth are poorly understood. In Drosophila melanogaster, growth ceases in response to a peak of the molting hormone ecdysone that coincides with a nutrition-dependent checkpoint, critical weight. Previous studies indicate that insulin/insulin-like growth factor signaling (IIS)/Target of Rapamycin (TOR) signaling in the prothoracic glands (PGs) regulates ecdysone biosynthesis and critical weight. Here we elucidate a mechanism through which this occurs. We show that Forkhead Box class O (FoxO), a negative regulator of IIS/TOR, directly interacts with Ultraspiracle (Usp), part of the ecdysone receptor. While overexpressing FoxO in the PGs delays ecdysone biosynthesis and critical weight, disrupting FoxO-Usp binding reduces these delays. Further, feeding ecdysone to larvae eliminates the effects of critical weight. Thus, nutrition controls ecdysone biosynthesis partially via FoxO-Usp prior to critical weight, ensuring that growth only stops once larvae have achieved a target nutritional status.