Tumor induction in Drosophila imaginal epithelia triggers modulation of fat body lipid droplets.

Our understanding of cancer-specific metabolic changes is currently unclear. In recent years, the fruit fly Drosophila melanogaster with its powerful genetic tools has become an attractive model for studying both tumor autonomous and the systemic processes resulting from the tumor growth. Here we investigated the effect of tumorigenesis on the modulation of lipid droplets (LDs) in the larval fat bodies (mammalian equivalent of adipose tissue). We have overexpressed Notch signaling alone or in combination with the developmental regulator Myocyte enhancer factor 2 (Mef2) using wing-specific and eye-specific drivers, quantified the size of LDs in the fat body of the different tumor bearing larvae, and estimated the expression of genes associated with lipolysis and lipogenesis. We have found that hyperplastic and neoplastic tumor induced by overexpression of Notch and co-expression of Notch and Mef2 respectively triggers impaired lipid metabolism marked by increased size of fat body LDs. The impaired lipid metabolism in tumor carrying larvae is linked to the altered expression of genes that participate in lipolysis and lipogenesis. These findings reveal modulation of LDs as one of the host's specific response upon tumor initiation. This information could potentially uncover mechanisms for designing innovative approaches to modulate cancer growth.

Gut bacteria-derived peptidoglycan induces a metabolic syndrome-like phenotype via NF-κB-dependent insulin/PI3K signaling reduction in Drosophila renal system.

Although microbiome-host interactions are usual at steady state, gut microbiota dysbiosis can unbalance the physiological and behavioral parameters of the host, mostly via yet not understood mechanisms. Using the Drosophila model, we investigated the consequences of a gut chronic dysbiosis on the host physiology. Our results show that adult flies chronically infected with the non-pathogenic Erwinia carotorova caotovora bacteria displayed organ degeneration resembling wasting-like phenotypes reminiscent of Metabolic Syndrome associated pathologies. Genetic manipulations demonstrate that a local reduction of insulin signaling consecutive to a peptidoglycan-dependent NF-κB activation in the excretory system of the flies is responsible for several of the observed phenotypes. This work establishes a functional crosstalk between bacteria-derived peptidoglycan and the immune NF-κB cascade that contributes to the onset of metabolic disorders by reducing insulin signal transduction. Giving the high degree of evolutionary conservation of the mechanisms and pathways involved, this study is likely to provide a helpful model to elucidate the contribution of altered intestinal microbiota in triggering human chronic kidney diseases.

Comet assay protocol for Bombus atratus fat body and pericardial cells (Hymenoptera, bombini) at a safe concentration of mercury.

The decline of the Bombus population is closely related to the presence of environmental pollutants. Among these pollutants, trace metals represent a major concern, which includes mercury, a known genotoxic substance. The induction of genotoxicity may be demonstrated by the comet assay (a.k.a. single-cell gel electrophoresis), a simple and sensitive method for DNA damage estimating. The current work provided, for the first time, a protocol of comet assay for Bombus atratus using mercury as a standard chemical at safe concentrations according to the Environment National Council of Brazil, and the World Health Organization. Bees were collected and divided into three groups (n = 11 each), in which the exposed groups received a 0.2 ppb or a 1 ppb of mercury solution, and the control group received water. The bioassay was performed for 48 h at controlled temperature and humidity conditions, according to the OECD guideline toxicological test method for B. terrestris. The samples were stained with different dyes to observe the efficacy of each one. Variations of parameters in methodology, such as concentration and time of exposure to lysis solution as well as the electrophoretic process, allowed the observation of comets at different levels. DAPI and acridine orange presented an unstable fluorescence, and silver nitrate dye was more effective. Therefore, the comet assay was shown to be an effective method to evaluate genotoxic effects in bees. The obtained results may be helpful for the establishment of a suitable protocol for future genotoxicity assessment in neotropical bees using different doses of xenobiotics.

Morphological and immunohistochemical study of the midgut and fat body of Spodoptera frugiperda (J.E. Smith) (Lepidoptera: noctuidae) treated with essential oils of the genus Piper.

Essential oils are a promising alternative to insecticides. We investigated the LD50 of oils extracted from Piper corcovadensis, P. marginatum, and P. arboreum after 48 h topical contact with Spodoptera frugiperda larvae using morphometry, histochemistry and immunohistochemistry of the midgut and fat body. Chromatography revealed that E-caryophyllene was the principal compound common to the Piper species. The essential oils of P. corcovadensis, P. marginatum and P. arboreum caused deleterious changes in the midgut of S. frugiperda larvae. P. corcovadensis oil produced the lowest LD50 and significant histopathological alterations including elongation of the columnar cells, formation of cytoplasmic protrusions, reduction in carbohydrate, increased apoptotic index and decreased cell proliferation. P. arboreum oil caused histopathological alterations similar to P. corcovadensis, but caused the highest rate of cell proliferation and increased regenerative cells, which indicated rapid regeneration of the epithelium. Our findings demonstrated the insecticidal potential of P. corcovadensis for control of S. frugiperda owing to the significant damage it inflicted on S. frugiperda midgut.

Fat body disintegration after freezing stress is a consequence rather than a cause of freezing injury in larvae of Drosophila melanogaster.

Extracellular freezing of insect body water may cause lethal injury either by direct mechanical stress exerted by growing ice crystals on cells and tissues or, indirectly, by deleterious physico-chemical effects linked to freeze-induced cell dehydration. Here we present results showing that the macroscopic damage (cell ruptures, tissue disintegration) to fat body of Drosophila melanogaster is not directly caused by mechanical forces linked to growth of ice crystals but rather represents a secondary consequence of other primary freeze injuries occurring at subcellular or microscopic levels. Larvae of D. melanogaster were acclimated to produce variants ranging from freeze susceptible to freeze tolerant. Then, larvae were exposed to supercooling and freezing stresses at different subzero temperatures. The larval survival and macroscopic damage to fat body tissue was scored in 1632 larvae exposed to cold stress. In most cases, fat body damage was not evident immediately following cold stress but developed later. This suggests that the fat body disintegration is a consequence rather than a cause of cold injury. Analysis of fat body membrane phospholipids revealed that increased freeze tolerance was associated with increased relative proportion of phosphatidylethanolamines (PEs) at the expense of phosphatidylcholines (PCs). The PE/PC ratio increased from 1.08 in freeze-susceptible larvae to 2.10 in freeze-tolerant larvae. The potential effects of changing PE/PC ratio on phospholipid bilayer stability upon supercooling and freezing stress are discussed.

The Exchangeable Apolipoprotein Nplp2 Sustains Lipid Flow and Heat Acclimation in Drosophila.

In ectotherms, increased ambient temperature requires the organism to consume substantial amounts of energy to sustain a higher metabolic rate, prevent cellular damage, and respond to heat stress. Here, we identify a heat-inducible apolipoprotein required for thermal acclimation in Drosophila. Neuropeptide-like precursor 2 (Nplp2) is an abundant hemolymphatic protein thought to be a neuropeptide. In contrast, we show that Nplp2 contributes to lipid transport, functioning as an exchangeable apolipoprotein. More precisely, Nplp2-deficient flies accumulate lipids in their gut, have reduced fat stores, and display a dyslipoproteinemia, showing that Nplp2 is required for dietary lipid assimilation. Importantly, Nplp2 is induced upon thermal stress and contributes to survival upon heat stress. We propose that Nplp2 associates with lipoprotein particles under homeostatic and high energy-demand conditions to optimize fat transport and storage. Our study also shows that modulation of the lipid uptake and transport machinery is part of an integrated cytoprotective response.

Insecticide activity of Curcuma longa (leaves) essential oil and its major compound α-phellandrene against Lucilia cuprina larvae (Diptera: Calliphoridae): Histological and ultrastructural biomarkers assessment.

Lucilia cuprina, known as the Australian blowfly, is of high medico-sanitary and veterinary importance due to its ability to induce myiasis. Synthetic products are the most frequent form of fly control, but their indiscriminate use has selected for resistant populations and accounted for high levels of residues in animal products. This study aimed to assess the effect of essential oil from leaves of Curcuma longa (CLLEO), and its major compound α-phellandrene against L. cuprina L3. An additional goal was to determine the morphological alterations in target organs/tissues through ultrastructural assessment (SEM) and light microscopy, as well as macroscopic damage to cuticle induced by CLLEO. Groups of 20 L3 were placed on filter paper impregnated with increasing concentrations of CLLEO (0.15 to 2.86 µL/cm2) and α-phellandrene (0.29 to 1.47 µL/cm2). Efficacy was determined by quantifying L3 mortality 6, 24 and 48 h after contact with CLLEO and by measuring the structural damage to L3. CLLEO and α-phellandrene inhibited adult emergence by 96.22 and 100%, respectively. Macroscopic cuticle damage, appeared as diffuse pigment and darkening of larval body, was caused by both extracts. The SEM revealed dryness on the cuticle surface, distortion of the sensorial structures and general degeneration in treated L3. Furthermore, alterations in target organs (digestive tract, fat body and brain) were noticed and shall be used as biomarkers in future attempts to elucidate the mechanism of action of these compounds. The vacuolar degeneration and pyknotic profiles observed in the brain tissue of treated larvae with both extracts and the decreased motility within <6 h after treatment leads us to suggest a neurotoxic activity of the products. This work demonstrates the potential use of CLLEO and α-phellandrene as bioinsecticides to be used against L. cuprina, representing an ecofriendly alternative for myiasis control in humans and animals.

Sublethal Effects of Solanum nigrum Fruit Extract and Its Pure Glycoalkaloids on the Physiology of Tenebrio molitor (Mealworm).

BACKGROUND: Solanaceae plants produce glycoalkaloids (GAs) that affect various physiological processes of herbivorous insects and they are being tested as potential alternatives for synthetic pesticides. They cause lethal and sublethal effects. Nevertheless, their mode of action remains unclear. Therefore, we examined the effects of Solanum nigrum fruit extracts and pure glycoalkaloids on a model beetle, Tenebrio molitor. METHODS: Plant extracts or pure alkaloids were added to the food of the larvae for three days. The lipid, glycogen, and protein content in the fat body and the midgut were determined, and the contractility of the heart, hindgut, and oviduct muscles was tested using the video-microscopy technique. Finally, the ultrastructure of the fat body and the midgut was observed using electron microscopy. RESULTS: No lethal effects were noted. Sublethal changes were observed in the content of biomolecules, malformations of organelles, chromatin condensation, and heart and oviduct contractility. The observed effects differed between the tested glycoalkaloids and the extract. CONCLUSIONS: Both the extract and pure GAs have a wide range of effects that may result in impaired development, food intake, and reproduction. Some early effects may be used as bioindicators of stress. The effects of the extract and pure alkaloids suggest that the substances produced by the plant may act additively or synergistically.

Comparative transcriptomics reveals CrebA as a novel regulator of infection tolerance in D. melanogaster.

Host responses to infection encompass many processes in addition to activation of the immune system, including metabolic adaptations, stress responses, tissue repair, and other reactions. The response to bacterial infection in Drosophila melanogaster has been classically described in studies that focused on the immune response elicited by a small set of largely avirulent microbes. Thus, we have surprisingly limited knowledge of responses to infection that are outside the canonical immune response, of how the response to pathogenic infection differs from that to avirulent bacteria, or even of how generic the response to various microbes is and what regulates that core response. In this study, we addressed these questions by profiling the D. melanogaster transcriptomic response to 10 bacteria that span the spectrum of virulence. We found that each bacterium triggers a unique transcriptional response, with distinct genes making up to one third of the response elicited by highly virulent bacteria. We also identified a core set of 252 genes that are differentially expressed in response to the majority of bacteria tested. Among these, we determined that the transcription factor CrebA is a novel regulator of infection tolerance. Knock-down of CrebA significantly increased mortality from microbial infection without any concomitant change in bacterial number. Upon infection, CrebA is upregulated by both the Toll and Imd pathways in the fat body, where it is required to induce the expression of secretory pathway genes. Loss of CrebA during infection triggered endoplasmic reticulum (ER) stress and activated the unfolded protein response (UPR), which contributed to infection-induced mortality. Altogether, our study reveals essential features of the response to bacterial infection and elucidates the function of a novel regulator of infection tolerance.

AMP-activated protein kinase protects against anoxia in Drosophila melanogaster.

During anoxia, proper energy maintenance is essential in order to maintain neural operation. Starvation activates AMP-activated protein kinase (AMPK), an evolutionarily conserved indicator of cellular energy status, in a cascade which modulates ATP production and consumption. We investigated the role of energetic status on anoxia tolerance in Drosophila and discovered that starvation or AMPK activation increases the speed of locomotor recovery from an anoxic coma. Using temporal and spatial genetic targeting we found that AMPK in the fat body contributes to starvation-induced fast locomotor recovery, whereas, under fed conditions, disrupting AMPK in oenocytes prolongs recovery. By evaluating spreading depolarization in the fly brain during anoxia we show that AMPK activation reduces the severity of ionic disruption and prolongs recovery of electrical activity. Further genetic targeting indicates that glial, but not neuronal, AMPK affects locomotor recovery. Together, these findings support a model in which AMPK is neuroprotective in Drosophila.

High fat diet-induced TGF-ß/Gbb signaling provokes insulin resistance through the tribbles expression.

Hyperglycemia, hyperlipidemia, and insulin resistance are hallmarks of obesity-induced type 2 diabetes, which is often caused by a high-fat diet (HFD). However, the molecular mechanisms underlying HFD-induced insulin resistance have not been elucidated in detail. In this study, we established a Drosophila model to investigate the molecular mechanisms of HFD-induced diabetes. HFD model flies recapitulate mammalian diabetic phenotypes including elevated triglyceride and circulating glucose levels, as well as insulin resistance. Expression of glass bottom boat (gbb), a Drosophila homolog of mammalian transforming growth factor-ß (TGF-ß), is elevated under HFD conditions. Furthermore, overexpression of gbb in the fat body produced obese and insulin-resistant phenotypes similar to those of HFD-fed flies, whereas inhibition of Gbb signaling significantly ameliorated HFD-induced metabolic phenotypes. We also discovered that tribbles, a negative regulator of AKT, is a target gene of Gbb signaling in the fat body. Overexpression of tribbles in flies in the fat body phenocopied the metabolic defects associated with HFD conditions or Gbb overexpression, whereas tribbles knockdown rescued these metabolic phenotypes. These results indicate that HFD-induced TGF-ß/Gbb signaling provokes insulin resistance by increasing tribbles expression.

Tratamento de fístula bucossinusal com o uso de retalho do corpo adiposo de Bichat û relato de caso / Treatment of oroantral communications using pedicled buccal fat pad graft û case report

Fístulas bucossinusais são comunicações epitelizadas entre o meio oral e o seio maxilar. Ocorrem principalmente como complicação de intervenções cirúrgicas orais e maxilofaciais. Pequenas comunicações geralmente são autorresolutivas, porém nas comunicações maiores, um tecido epitelial pode desenvolver-se em torno do seu trajeto, configurando, assim, uma fístula bucossinusal. Vários métodos de tratamento para fístula bucossinusal têm sido descritos na literatura. Devido à facilidade de acesso e rico suprimento sanguíneo, o corpo adiposo bucal é adequado para obliteração de defeitos posteriores da maxila, tanto na região de palato duro e mole, como na região alveolar e retromolar. Este trabalho objetiva relatar o caso clínico de uma fístula bucossinusal na região de rebordo alveolar maxilar esquerdo proveniente de um procedimento cirúrgico para levantamento de seio maxilar realizado há dois meses. Foi realizada antibioticoterapia para controle da infecção sinusal e tratamento cirúrgico da fístula pela técnica de retalho pediculado do corpo adiposo de Bichat, onde o mesmo foi dissecado, fracionado para a área comprometida e estabilizado à mucosa adjacente. A paciente encontra-se em acompanhamento há um ano sem queixas e/ou sinais de recidiva...

Oroantral fistula are epithelized communications between the oral environment and the maxillary sinus. They occur mainly as a complication of oral and maxillofacial surgery. Small communications are usually self resolving, but in major communications, an epithelial tissue can develop around your path, so setting a oroantral fistula. Various methods of treatment for buccal sinus fistula have been described in literature. Due to the ease of access and rich blood supply, the buccal fat pad is suitable for obliteration of later defects of the jaw, both in the area of hard and soft palate, as in alveolar and retromolar region. This is a case report of a oroantral fistula on the left maxillary alveolar region from a surgical procedure to maxillary sinus survey conducted two months ago. Antibiotic therapy was performed to control sinus infection and surgical treatment of fistula by pedicle flap technique of the fat pad of Bichat, where it was dissected, split to the affected area, and stabilized to the adjacent mucosa. The patient has been followed for a year without complaints and/or signs of recurrence...

Histopathological changes in the perivisceral fat body of Rhinocricus padbergi (Diplopoda, Spirobolida) triggered by biosolids.

Human activities generate a great amount of sewage daily, which is dumped into the sewer system. After sewage-treatment processes, sewage sludge is generated. Such byproduct can be treated by different methods; the result of treatment is a stabilized compost of reduced pathogenicity that has a similar inorganic chemical composition to the raw sewage sludge. After such pretreatment, sewage sludge is called a biosolids, and it can be used in agriculture. In this contest, the present study evaluated the effects of a sample of biosolids on the perivisceral fat body of a diplopod. These invertebrates are soil organisms that play an important role in the dynamics of terrestrial ecosystems, and as a consequence, they are in contact with xenobiotics present in this environmental compartment. Special emphasis is given on the interpretation of the effects of complex mixtures in target organs of diplopods. A semiquantitative analysis for the evaluation of histopathological changes in the perivisceral fat body was proposed. The sample-induced histopathological and ultrastructural changes in individuals exposed to it, and the severity of the effects was positively related to the exposure time, resulting in the deaths of exposed individuals after 90 days. Thus, the results indicate the need for caution in the use of biosolids as well as the need for improving waste management techniques, so they will produce environmentally innocuous final products.

Local and systemic effects of targeted zinc redistribution in Drosophila neuronal and gastrointestinal tissues.

While the effects of systemic zinc ion deficiency and toxicity on animal health are well documented, the impacts of localized, tissue-specific disturbances in zinc homeostasis are less well understood. Previously we have identified zinc dyshomeostasis scenarios caused by the targeted manipulation of zinc transport genes in the Drosophila eye. Over expression of the uptake transporter dZIP42C.1 (dZIP1) combined with knockdown of the efflux transporter dZNT63C (dZNT1) causes a zinc toxicity phenotype, as does over expression of dZIP71B or dZNT86D. However, all three genotypes result in different morphologies, responses to dietary zinc, and genetic interactions with the remaining zinc transport genes, indicating that each causes a different redistribution of zinc within affected cells. dZNT86D (eGFP) over expression generates a completely different phenotype, interpreted as a Golgi zinc deficiency. Here we assess the effect of each of these transgenes when targeted to a range of Drosophila tissues. We find that dZIP71B is a particularly potent zinc uptake gene, causing early developmental lethality when targeted to multiple different tissue types. dZNT86D over expression (Golgi-only zinc toxicity) is less deleterious, but causes highly penetrant adult cuticle, sensory bristle and wing expansion defects. The dZIP42C.1 over expression, dZNT63C knockdown combination causes only moderate adult cuticle defects and sensitivity to dietary zinc when expressed in the midgut. The Golgi-only zinc deficiency caused by dZNT86D (eGFP) expression results in mild cuticle defects, highly penetrant wing expansion defects and developmental lethality when targeted to the central nervous system and, uniquely, the fat bodies.

Transcriptional response of two metallothionein genes (OcMT1 and OcMT2) and histological changes in Oxya chinensis (Orthoptera: Acridoidea) exposed to three trace metals.

This study evaluated the transcriptional responses of two metallothionein (MT) genes (OcMT1 and OcMT2) in various tissues (brain, optic lobe, Malpighian tubules, fat bodies, foregut, gastric caeca, midgut and hindgut) of Oxya chinensis (Thunberg) (Orthoptera: Acridoidea) after exposed to the trace metals cadmium (Cd), copper (Cu) and zinc (Zn) for 48h. The study revealed that the exposure of O. chinensis to each of the three metals at the median lethal concentration (LC50) or lower concentration(s) up-regulated the transcriptions of both OcMT1 and OCMT2 in the eight tissues except for OcMT1 and OcMT2 with Cd in brain and gastric caeca, respectively, and OcMT2 with Cu in gastric caeca. These results suggested that the exposure of O. chinensis to the metals may enhance MT biosynthesis that protects tissues by binding these metals in various tissues. To examine possible histopathological effect of the metals, we examined the histological changes in the fat bodies after O. chinensis was exposed to each of these metals at LC50. The exposure of Cd significantly reduced the size and number of adipocytes as compared with the control. However, such an effect was not observed in O. chinensis exposed to either Cu or Zn. These results suggested that fat bodies might be either significantly affected by Cd or play a crucial role in detoxification of excessive trace metals.

Lamin-B in systemic inflammation, tissue homeostasis, and aging.

Gradual loss of tissue function (or homeostasis) is a natural process of aging and is believed to cause many age-associated diseases. In human epidemiology studies, the low-grade and chronic systemic inflammation in elderly has been correlated with the development of aging related pathologies. Although it is suspected that tissue decline is related to systemic inflammation, the cause and consequence of these aging phenomena are poorly understood. By studying the Drosophila fat body and gut, we have uncovered a mechanism by which lamin-B loss in the fat body upon aging induces age-associated systemic inflammation. This chronic inflammation results in the repression of gut local immune response, which in turn leads to the over-proliferation and mis-differentiation of the intestinal stem cells, thereby resulting in gut hyperplasia. Here we discuss the implications and remaining questions in light of our published findings and new observations.

A Drosophila functional evaluation of candidates from human genome-wide association studies of type 2 diabetes and related metabolic traits identifies tissue-specific roles for dHHEX.

BACKGROUND: Genome-wide association studies (GWAS) identify regions of the genome that are associated with particular traits, but do not typically identify specific causative genetic elements. For example, while a large number of single nucleotide polymorphisms associated with type 2 diabetes (T2D) and related traits have been identified by human GWAS, only a few genes have functional evidence to support or to rule out a role in cellular metabolism or dietary interactions. Here, we use a recently developed Drosophila model in which high-sucrose feeding induces phenotypes similar to T2D to assess orthologs of human GWAS-identified candidate genes for risk of T2D and related traits. RESULTS: Disrupting orthologs of certain T2D candidate genes (HHEX, THADA, PPARG, KCNJ11) led to sucrose-dependent toxicity. Tissue-specific knockdown of the HHEX ortholog dHHEX (CG7056) directed metabolic defects and enhanced lethality; for example, fat-body-specific loss of dHHEX led to increased hemolymph glucose and reduced insulin sensitivity. CONCLUSION: Candidate genes identified in human genetic studies of metabolic traits can be prioritized and functionally characterized using a simple Drosophila approach. To our knowledge, this is the first large-scale effort to study the functional interaction between GWAS-identified candidate genes and an environmental risk factor such as diet in a model organism system.

Biochemical and histological effects of gibberellic acid on Locusta migratoria migratoria fifth instar larvae.

Experiments were conducted to assess the effect of gibberellic acid (GA3), a plant growth regulator, on Locusta migratoria migratoria fifth instar larvae. Newly emerged larvae were exposed to various concentrations of GA3 administered by topical application or by forced ingestion. Results showed that treated insects exhibited toxic symptoms with a dose-dependent mortality. GA3 toxicity was also demonstrated by perturbation of the moult processes. In fact, we noted that treated insects present exuviations difficulties due to the impossibility to reject the old integuments causing mortality in the 5th instar larvae. Histological study of proventriculus revealed alterations in the epithelial cells and absence of apolysis phenomenon. Data also showed that GA3 induced significant quantitative variation of haemolymph metabolites. These changes result in a significant decrease in the total concentration of proteins and carbohydrates and an increase in the total concentration of haemolymph lipids.

The laryngeal fat body.

AIM: To describe the anatomy and topography of the laryngeal fat body and of the space it lies within. MATERIALS AND METHODS: The study is carried out on series of histological sections of head and neck blocks from six foetuses and three newborns. Three adult necks were dissected, a fourth one analysed through sagittal median section. CT-Scan and MRI imaging complete the description. RESULTS: The laryngeal fat body (LFB) lies within the pre-epiglottic (PE) space that stands in the median anterior part of the upper infrahyoid region, located just below the level of the hyoid bone. The walls of the PE space are: superior (base), anterior lateral right and left, posterior, inferior (apex). This space is divided into two compartments by a median septum. The LFB consists in a rather pure fat, structured in large polyhedral lobules. It shows no limiting capsule. DISCUSSION: Dissection-based description of the PE space made in literature matches ours conducted on series of histological sections. All authors agree on the fat content of the space but some of them find a capsule around the LFB that we did not observe on our histological sections. CT-Scan and MRI imaging are accurate for analysis of these structures and of similar efficiency. The study of the LFB should be considered regarding the one of other fat bodies in the human body. CONCLUSION: Anatomical knowledge of the PE space and its content, the LFB, is important, as alteration of their morphology is the early witness of neighbouring carcinological extension.

Gbb/BMP signaling is required to maintain energy homeostasis in Drosophila.

The coordination of animal growth and development requires adequate nutrients. During times of insufficient food, developmental progression is slowed and stored energy is utilized to ensure that cell and tissue survival are maintained. Here, we report our finding that the Gbb/BMP signaling pathway, known to play an important role in many developmental processes in both vertebrates and invertebrates, is critical in the Drosophila larval fat body for regulating energy homeostasis. Animals with mutations in the Drosophila BMP-5,7 orthologue, glass bottom boat (gbb), or in its signaling components, display phenotypes similar to nutrient-deprived and Tor mutant larvae. These phenotypes include a developmental delay with reduced overall growth, a transparent appearance, and altered total lipid, glucose and trehalose levels. We find that Gbb/BMP signaling is required in the larval fat body for maintaining proper metabolism, yet interestingly, following nutrient deprivation larvae in turn show a loss of BMP signaling in fat body cells indicating that Gbb/BMP signaling is a central player in homeostasis. Finally, despite strong phenotypic similarities between nutrient-compromised animals and gbb mutants, distinct differences are observed in the expression of a group of starvation responsive genes. Overall, our results implicate Gbb/BMP signaling as a new pathway critical for positive regulation of nutrient storage and energy homeostasis during development.