Being overweight increases the risk of many metabolic disorders, but how it affects lifespan is not completely clear. Not all obese people become ill, and the exact mechanism that turns excessive fat storage into a health-threatening state remains unknown. Drosophila melanogaster has served as an excellent model for many diseases, including obesity, diabetes, and hyperglycemia-associated disorders, such as cardiomyopathy or nephropathy. Here, we review the connections between fat storage and aging in different types of fly obesity. Whereas obesity induced by high-fat or high-sugar diet is associated with hyperglycemia, cardiomyopathy, and in some cases, shortening of lifespan, there are also examples in which obesity correlates with longevity. Transgenic lines with downregulations of the insulin/insulin-like growth factor (IIS) and target of rapamycin (TOR) signaling pathways, flies reared under dietary restriction, and even certain longevity selection lines are obese, yet long-lived. The mechanisms that underlie the differential lifespans in distinct types of obesity remain to be elucidated, but fat turnover, inflammatory pathways, and dysregulations of glucose metabolism may play key roles. Altogether, Drosophila is an excellent model to study the physiology of adiposity in both health and disease.

Animals need to continuously adjust their water metabolism to the internal and external conditions. Homeostasis of body fluids thus requires tight regulation of water intake and excretion, and a balance between ingestion of water and solid food. Here, we investigated how these processes are coordinated in Drosophila melanogaster. We identified the first thirst-promoting and anti-diuretic hormone of Drosophila, encoded by the gene Ion transport peptide (ITP). This endocrine regulator belongs to the CHH (crustacean hyperglycemic hormone) family of peptide hormones. Using genetic gain- and loss-of-function experiments, we show that ITP signaling acts analogous to the human vasopressin and renin-angiotensin systems; expression of ITP is elevated by dehydration of the fly, and the peptide increases thirst while repressing excretion, promoting thus conservation of water resources. ITP responds to both osmotic and desiccation stress, and dysregulation of ITP signaling compromises the fly’s ability to cope with these stressors. In addition to the regulation of thirst and excretion, ITP also suppresses food intake. Altogether, our work identifies ITP as an important endocrine regulator of thirst and excretion, which integrates water homeostasis with feeding of Drosophila. Maintenance of energy and water balance is necessary for survival of all organisms. Even a mild dehydration triggers thirst, reduces appetite, and decreases diuresis (water excretion), thereby promoting conservation of water resources and survival under arid conditions. Homeostasis is regulated primarily by endocrine systems that utilize neuropeptides and peptide hormones. Whereas hormonal mechanisms that regulate the water balance in humans are relatively well understood, much less is known about these regulations in the fruit fly Drosophila melanogaster. Here, we describe the first thirst-promoting and anti-diuretic hormone of Drosophila, encoded by the gene Ion transport peptide (ITP). We show that ITP increases upon dehydration, and protects the animal from loss of body water by promoting thirst and repressing excretion. ITP also suppresses feeding, and can thus be considered as a master regulator integrating water and energy balance.

Temperature has a profound impact on animal physiology. In this study, we examined the effect of ambient temperature on the energy stores of the model organismDrosophila melanogaster. By exposing adult males to 11 temperatures between 13 °C and 33 °C, we found that temperature significantly affects the amount of energy reserves. Whereas flies increase their fat stores at intermediate temperatures, exposure to temperatures below 15 °C or above 27 °C causes a reduction of fat reserves. Moreover, we found that glycogen stores followed a similar trend, although not so pronounced. To elucidate the underlying mechanism of these changes, we compared the temperature dependence of food consumption and metabolic rate. This analysis revealed that food intake and metabolic rate scale with temperature equally, suggesting that the temperature-induced changes in energy reserves are probably not caused by a mismatch between these two traits. Finally, we assessed the effect of temperature on starvation resistance. We found that starvation survival is a negative exponential function of temperature; however we did not find any clear evidence that implies the relative starvation resistance is compromised at non-optimal temperatures. Our results indicate that whilst optimal temperatures can promote accumulation of energy reserves, exposure to non-optimal temperatures reducesDrosophilaenergy stores.

In mammals, energy homeostasis is regulated by the antagonistic action of hormones insulin and glucagon. However, in contrast to the highly conserved insulin, glucagon is absent in most invertebrates. Although there are several endocrine regulators of energy expenditure and catabolism (such as the adipokinetic hormone), no single invertebrate hormone with all of the functions of glucagon has been described so far. Here, we used genetic gain- and loss-of-function experiments to show that the Drosophila gene Ion transport peptide (ITP) codes for a novel catabolic regulator that increases energy expenditure, lowers fat and glycogen reserves, and increases glucose and trehalose. Intriguingly, Ion transport peptide has additional functions reminiscent of glucagon, such as inhibition of feeding and transit of the meal throughout the digestive tract. Furthermore, Ion transport peptide interacts with the well-known signaling via the Adipokinetic hormone; Ion transport peptide promotes the pathway by stimulating Adipokinetic hormone secretion and transcription of the receptor AkhR. The genetic manipulations of Ion transport peptide on standard and Adipokinetic hormone-deficient backgrounds showed that the Adipokinetic hormone peptide mediates the hyperglycemic and hypertrehalosemic effects of Ion transport peptide, while the other metabolic functions of Ion transport peptide seem to be Adipokinetic hormone independent. In addition, Ion transport peptide is necessary for critical processes such as development, starvation-induced foraging, reproduction, and average lifespan. Altogether, our work describes a novel master regulator of fly physiology with functions closely resembling mammalian glucagon.