Lipid droplet-based storage fat metabolism in Drosophila.

The fruit fly Drosophila melanogaster is an emerging model system in lipid metabolism research. Lipid droplets are omnipresent and dynamically regulated organelles found in various cell types throughout the complex life cycle of this insect. The vital importance of lipid droplets as energy resources and storage compartments for lipoanabolic components has recently attracted research attention to the basic enzymatic machinery, which controls the delicate balance between triacylglycerol deposition and mobilization in flies. This review aims to present current insights in experimentally supported and inferred biological functions of lipogenic and lipolytic enzymes as well as regulatory proteins, which control the lipid droplet-based storage fat turnover in Drosophila

Gαq, Gγ1 and Plc21C control Drosophila body fat storage.

Adaptive mobilization of body fat is essential for energy homeostasis in animals. In insects, the adipokinetic hormone (Akh) systemically controls body fat mobilization. Biochemical evidence supports that Akh signals via a G protein-coupled receptor (GPCR) called Akh receptor (AkhR) using cyclic-AMP (cAMP) and Ca2+ second messengers to induce storage lipid release from fat body cells. Recently, we provided genetic evidence that the intracellular calcium (iCa2+) level in fat storage cells controls adiposity in the fruit fly Drosophila melanogaster. However, little is known about the genes, which mediate Akh signalling downstream of the AkhR to regulate changes in iCa2+. Here, we used thermogenetics to provide in vivo evidence that the GPCR signal transducers G protein α q subunit (Gαq), G protein γ1 (Gγ1) and Phospholipase C at 21C (Plc21C) control cellular and organismal fat storage in Drosophila. Transgenic modulation of Gαq, Gγ1 and Plc21C affected the iCa2+ of fat body cells and the expression profile of the lipid metabolism effector genes midway and brummer, which results in severely obese or lean flies. Moreover, functional impairment of Gαq, Gγ1 and Plc21C antagonised Akh-induced fat depletion. This study characterizes Gαq, Gγ1 and Plc21C as anti-obesity genes and supports the model that Akh employs the Gαq/Gγ1/Plc21C module of iCa2+ control to regulate lipid mobilization in adult Drosophila

The obesity-related adipokinetic hormone controls feeding and expression of neuropeptide regulators of Drosophila metabolism.

Homeostasis of circulating and storage energy reserves in mammals is dependent on the antagonistically acting insulin and glucagon signaling. In the model organism Drosophila melanogaster, this function is executed by the insulin-like peptides and the glucagon-like Adipokinetic hormone (AKH). Loss of Drosophila AKH results in the adulthood-specific onset of obesity coupled with hypoglycemia. However, apart from the role of AKH in the lipid mobilization, the physiological and endocrine underpinnings of the AKH deficiency-triggered obesity are unknown. Here, we investigate the role of AKH in feeding and metabolic rate control, and address the interactions of this hormone with other endocrine regulators of fly metabolism. Via in vivo gain- and loss-of-function analyses, we show that despite its anti-obesity effects, AKH is an orexigenic peptide. Moreover, AKH also affects expression of orexigenic factors CCHamide-2 and neuropeptide F. In addition, AKH regulates metabolic genes like Corazonin, Limostatin, and Insulin-like peptides (Ilps) 2, 3, 5, and 6. Altogether, our work shows that the Drosophila AKH is a central regulator of energy homeostasis; next to its well-known role in the control of energy expenditure, this hormone controls also food intake, and expression of other endocrine regulators of fly metabolism. Practical applications: Basic research of the neuroendocrine regulation of metabolism in the fruit fly D. melanogaster has potential applications in both human medicine and insect pest control. The evolutionary conservation of the key metabolic pathways, together with the unprecedented choice of transgenic tools turned the fruit fly into a useful model to study human diseases, including obesity and diabetes. Based on the evolutionary conservation of AKH and glucagon functions, our investigations might provide useful hints regarding the physiological actions, and endocrine interactions of human glucagon, too. In addition, insect neuropeptides are emerging as important targets for the parasite and pest control; understanding of their regulatory networks has thus potential implications also in the development of novel insecticides

Thermal stress depletes energy reserves in Drosophila.

Understanding how environmental temperature affects metabolic and physiological functions is of crucial importance to assess the impacts of climate change on organisms. Here, we used different laboratory strains and a wild-caught population of the fruit fly Drosophila melanogaster to examine the effect of temperature on the body energy reserves of an ectothermic organism. We found that permanent ambient temperature elevation or transient thermal stress causes significant depletion of body fat stores. Surprisingly, transient thermal stress induces a lasting “memory effect” on body fat storage, which also reduces survivorship of the flies upon food deprivation later after stress exposure. Functional analyses revealed that an intact heat-shock response is essential to protect flies from temperature-dependent body fat decline. Moreover, we found that the temperature-dependent body fat reduction is caused at least in part by apoptosis of fat body cells, which might irreversibly compromise the fat storage capacity of the flies. Altogether, our results provide evidence that thermal stress has a significant negative impact on organismal energy reserves, which in turn might affect individual fitness

Opposite and redundant roles of the two Drosophila perilipins in lipid mobilization.

Lipid droplets are the main lipid storage sites in cells. Lipid droplet homeostasis is regulated by the surface accessibility of lipases. Mammalian adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are two key lipases for basal and stimulated lipolysis, respectively. Perilipins, the best known lipid droplet surface proteins, can either recruit lipases or prevent the access of lipases to lipid droplets. Mammals have five perilipin proteins, which often exhibit redundant functions, precluding the analysis of the exact role of individual perilipins in vivo. Drosophila have only two perilipins, PLIN1/LSD-1 and PLIN2/LSD-2. Previous studies revealed that PLIN2 is important for protecting lipid droplets from lipolysis mediated by Brummer (BMM), the Drosophila homolog of ATGL. In this study, we report the functional analysis of PLIN1 and Drosophila HSL. Loss-of-function and overexpression studies reveal that unlike PLIN2, PLIN1 probably facilitates lipid mobilization. HSL is recruited from the cytosol to the surface of lipid droplets under starved conditions and PLIN1 is necessary for the starved induced lipid droplet localization of HSL. Moreover, phenotypic analysis of plin1;plin2 double mutants revealed that PLIN1 and PLIN2 might have redundant functions in protecting lipid droplets from lipolysis. Therefore, the two Drosophila perilipins have both opposite and redundant roles. Domain swapping and deletion analyses indicate that the C-terminal region of PLIN1 confers functional specificity to PLIN1. Our study highlights the complex roles of Drosophila perilipin proteins and the evolutionarily conserved regulation of HSL translocation by perilipins

csal1 Is Controlled by a Combination of FGF and Wnt Signals in Developing Limb Buds

While some of the signaling molecules that govern establishment of the limb axis have been characterized, little is known about the downstream effector genes that interpret these signals. In Drosophila, the spalt gene is involved in cell fate determination and pattern formation in different tissues. We have cloned a chick homologue of Drosophila spalt, which we have termed csal1, and this study focuses on the regulation of csal1 expression in the limb bud. csal1 is expressed in limb buds from HH 17 to 26, in both the apical ectodermal ridge and the distal mesenchyme. Signals from the apical ridge are essential for csal1 expression, while the dorsal ectoderm is required for csal1 expression at a distance from the ridge. Our data indicate that both FGF and Wnt signals are required for the regulation of csal1 expression in the limb. Mutations in the human homologue of csal1, termed Hsal1/SALL1, result in a condition known as Townes–Brocks syndrome (TBS), which is characterized by preaxial polydactyly. The developmental expression of csal1 together with the digit phenotype in TBS patients suggests that csal1 may play a role in some aspects of distal patterning

An exploration into the client at the heart of therapy : a qualitative perspective

Over 50 years ago Eysenck challenged the existing base of research into psychotherapy. Since that time, a large number of investigations have been conducted to verify the efficacy of therapy. Recently however, an increasing number of studies have cast new doubts on this research base. Instead of therapy being a function of the therapist, it is now becoming ever more apparent that the client plays a prime role in the therapeutic process. The qualitative studies presented in this paper provide some examples of research that demonstrates that clients are actively involved in their therapy, even making counselling work despite their counsellor. These studies suggest that clients may not experience therapy as beneficially as traditional outcome studies indicate. This raises a new challenge to researchers to more fully explore the client's experience of therapy, a challenge to which qualitative methods of inquiry would appear well suited