scholarly journals Regulation of Fat Cell Mass by Insulin in Drosophila melanogaster

2009 ◽  
Vol 29 (24) ◽  
pp. 6341-6352 ◽  
Author(s):  
Justin R. DiAngelo ◽  
Morris J. Birnbaum
Keyword(s):  
Drosophila Melanogaster ◽  
Insulin Signaling ◽  
Fat Body ◽  
Glycogen Synthase ◽  
Cell Mass ◽  
Fruit Fly ◽  
Cell Number ◽  
Fat Cell ◽  
Positive Effects ◽  
Adipocyte Cell

ABSTRACT A phylogenetically conserved response to nutritional abundance is an increase in insulin signaling, which initiates a set of biological responses dependent on the species. Consequences of augmented insulin signaling include developmental progression, cell and organ growth, and the storage of carbohydrates and lipids. Here, we address the evolutionary origins of insulin's positive effects on anabolic lipid metabolism by selectively modulating insulin signaling in the fat body of the fruit fly, Drosophila melanogaster. Analogous to the actions of insulin in higher vertebrates, those in Drosophila include expansion of the insect fat cell mass both by increasing the adipocyte number and by promoting lipid accumulation. The ability of insulin to accomplish the former depends on its capacity to bring about phosphorylation and inhibition of the transcription factor Drosophila FOXO (dFOXO) and the serine/threonine protein kinase shaggy, the fly ortholog of glycogen synthase kinase 3 (GSK3). Increasing the amount of triglyceride per cell also depends on the phosphorylation of shaggy but is independent of dFOXO. Thus, the findings of this study provide evidence that the control of fat mass by insulin is a conserved process and place dFOXO and shaggy/GSK3 downstream of the insulin receptor in controlling adipocyte cell number and triglyceride storage, respectively.

scholarly journals The use of Drosophila Melanogaster as a Model Organism to study the effect of Innate Immunity on Metabolism

2020 ◽  
Author(s):  
Abeer Mohbeddin ◽  
Nawar Haj Ahmed ◽  
Layla Kamareddine
Keyword(s):  
Drosophila Melanogaster ◽  
Fat Body ◽  
Model Organism ◽  
Fruit Fly ◽  
Janus Kinase ◽  
Signal Transducer ◽  
Metabolic Homeostasis ◽  
Stat Signaling ◽  
Stat Pathway

Apart from its traditional role in disease control, recent body of evidence has implicated a role of the immune system in regulating metabolic homeostasis. Owing to the importance of this “immune-metabolic alignment” in dictating a state of health or disease, a proper mechanistic understanding of this alignment is crucial in opening up for promising therapeutic approaches against a broad range of chronic, metabolic, and inflammatory disorders like obesity, diabetes, and inflammatory bowel syndrome. In this project, we addressed the role of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) innate immune pathway in regulating different metabolic parameters using the Drosophila melanogaster (DM) fruit fly model organism. Mutant JAK/STAT pathway flies with a systemic knockdown of either Domeless (Dome) [domeG0282], the receptor that activates JAK/STAT signaling, or the signal-transducer and activator of transcription protein at 92E (Stat92E) [stat92EEY10528], were used. The results of the study revealed that blocking JAK/STAT signaling alters the metabolic profile of mutant flies. Both domeG0282 and stat92EEY10528 mutants had an increase in body weight, lipid deprivation from their fat body (lipid storage organ in flies), irregular accumulation of lipid droplets in the gut, systemic elevation of glucose and triglyceride levels, and differential down-regulation in the relative gene expression of different peptide hormones (Tachykinin, Allatostatin C, and Diuretic hormone 31) known to regulate metabolic homeostasis in flies. Because the JAK/STAT pathway is evolutionary conserved between invertebrates and vertebrates, our potential findings in the fruit fly serves as a platform for further immune-metabolic translational studies in more complex mammalian systems including humans.

scholarly journals Sexual Dimorphism in Metabolic Responses to Western Diet in Drosophila melanogaster

Biomolecules ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 33
Author(s):  
Sofie De Groef ◽  
Tom Wilms ◽  
Séverine Balmand ◽  
Federica Calevro ◽  
Patrick Callaerts
Keyword(s):  
Drosophila Melanogaster ◽  
Sexual Dimorphism ◽  
Lipid Content ◽  
Fat Body ◽  
Fruit Fly ◽  
Fruit Flies ◽  
Standard Diet ◽  
Expression Of Genes ◽  
Obesogenic Diet ◽  
Ovarian Size

Obesity is a chronic disease affecting millions of people worldwide. The fruit fly (Drosophila melanogaster) is an interesting research model to study metabolic and transcriptomic responses to obesogenic diets. However, the sex-specific differences in these responses are still understudied and perhaps underestimated. In this study, we exposed adult male and female Dahomey fruit flies to a standard diet supplemented with sugar, fat, or a combination of both. The exposure to a diet supplemented with 10% sugar and 10% fat efficiently induced an increase in the lipid content in flies, a hallmark for obesity. This increase in the lipid content was more prominent in males, while females displayed significant changes in the glycogen content. The strong effects of the diets on the ovarian size and number of mature oocytes were also present in females exposed to diets supplemented with fat and a combination of fat and sugar. In both males and females, the fat body morphology changed and was associated with an increase in the lipid content of fat cells in response to the diets. The expression of metabolism-related genes also displayed a strong sexually dimorphic response under normal conditions and in response to the sugar and/or fat-supplemented diets. Here, we showed that the exposure of adult fruit flies to an obesogenic diet containing both sugar and fat allowed studying sexual dimorphism in metabolism and the expression of genes regulating metabolism.

scholarly journals Furbellow (Brown Algae) Extract Increases Lifespan in Drosophila by Interfering with TOR-Signaling

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1172
Author(s):  
Yang Li ◽  
Renja Romey-Glüsing ◽  
Navid Tahan Zadeh ◽  
Jakob von Frieling ◽  
Julia Hoffmann ◽  
...  
Keyword(s):  
Insulin Signaling ◽  
Brown Algae ◽  
Molecular Mechanisms ◽  
Fruit Fly ◽  
Tor Signaling ◽  
Signaling Systems ◽  
Positive Effects ◽  
Saccorhiza Polyschides ◽  
Health Promoting ◽  
Algal Products

Algal products are well known for their health promoting effects. Nonetheless, an in depth understanding of the underlying molecular mechanisms is still only fragmentary. Here, we show that aqueous furbelow extracts (brown algae, Saccorhiza polyschides) lengthen the life of both sexes of the fruit fly Drosophila melanogaster substantially, if used as nutritional additives to conventional food. This life prolonging effect became even more pronounced in the presence of stressors, such as high-fat dieting of living under drought conditions. Application of the extracts did not change food intake, excretion, or other major physiological parameters. Nevertheless, effects on the intestinal microbiota were observed, leading to an increased species richness, which is usually associated with healthy conditions. Lifespan extension was not observed in target of rapamycin (TOR)-deficient animals, implying that functional TOR signaling is necessary to unfold the positive effects of brown algae extract (BAE) on this important trait. The lack of life lengthening in animals with deregulated TOR signaling exclusively targeted to body fat showed that this major energy storage organ is instrumental for transmitting these effects. In addition, expression of Imaginal morphogenesis protein-Late 2 (Imp-L2), an effective inhibitor of insulin signaling implies that BAE exerts their positive effects through interaction with the tightly interwoven TOR- and insulin-signaling systems, although insulin levels were not directly affected by this intervention.

scholarly journals Chronobiotics KL001 and KS15 Extend Lifespan and Modify Circadian Rhythms of Drosophila melanogaster

2021 ◽  
Vol 3 (3) ◽  
pp. 429-441
Author(s):  
Ilya A. Solovev ◽  
Mikhail V. Shaposhnikov ◽  
Alexey A. Moskalev
Keyword(s):  
Drosophila Melanogaster ◽  
Locomotor Activity ◽  
Circadian Rhythms ◽  
Molecular Mechanisms ◽  
Fat Body ◽  
Young Male ◽  
Constant Darkness ◽  
Starvation Resistance ◽  
Positive Effects ◽  
Median Lifespan

Chronobiotics are a group of drugs, which are utilized to modify circadian rhythms targeting clock-associated molecular mechanisms. The circadian clock is known as a controller of numerous processes in connection with aging. Hypothesis: KL001 and KS15 targeting CRY, affect lifespan, locomotor activity and circadian rhythm of Drosophila melanogaster. We observed a slight (2%, p < 0.001) geroprotective effect on median lifespan (5 µM solution of KL001 in 0.1% DMSO) and a 14% increase in maximum lifespan in the same group. KS15 10 µM solution extended males’ median lifespan by 8% (p < 0.05). The statistically significant positive effects of KL001 and KS15 on lifespan were not observed in female flies. KL001 5 µM solution improved locomotor activity in young male imagoes (p < 0.05), elevated morning activity peak in aged imagoes and modified robustness of their circadian rhythms, leaving the period intact. KS15 10 µM solution decreased the locomotor activity in constant darkness and minimized the number of rhythmic flies. KL001 5 µM solution improved by 9% the mean starvation resistance in male flies (p < 0.01), while median resistance was elevated by 50% (p < 0.0001). This phenomenon may suggest the presence of the mechanism associated with improvement of fat body glucose depos’ utilization in starvation conditions which is activated by dCRY binding KL001.

scholarly journals The Drosophila melanogaster Metabolic Response against Parasitic Nematode Infection Is Mediated by TGF-β Signaling

2020 ◽  
Vol 8 (7) ◽  
pp. 971
Author(s):  
Yaprak Ozakman ◽  
Trishya Pagadala ◽  
Dhaivat Raval ◽  
Ioannis Eleftherianos
Keyword(s):  
Drosophila Melanogaster ◽  
Transforming Growth Factor ◽  
Metabolic Response ◽  
Fat Body ◽  
Sugar Metabolism ◽  
Fruit Fly ◽  
Transforming Growth Factor Β ◽  
Nematode Infection ◽  
Bmp Signaling ◽  
Host Metabolism

The nematode Heterorhabditis bacteriophora, its mutualistic bacterium Photorhabdus luminescens, and the fruit fly Drosophila melanogaster establish a unique system to study the basis of infection in relation to host metabolism. Our previous results indicate that the Transforming Growth Factor β (TGF-β) signaling pathway participates in the D. melanogaster metabolic response against nematode parasitism. However, our understanding of whether the presence of Photorhabdus bacteria in Heterorhabditis nematodes affects the metabolic state of D. melanogaster during infection is limited. Here, we investigated the involvement of TGF-β signaling branches, Activin and Bone Morphogenetic Protein (BMP), in the D. melanogaster metabolic response against axenic (lacking bacteria) or symbiotic (containing bacteria) H. bacteriophora infection. We show that BMP signaling mediates lipid metabolism against axenic or symbiotic H. bacteriophora and alters the size of fat body lipid droplets against symbiotic nematode infection. Also, following symbiotic H. bacteriophora infection, Activin signaling modulates sugar metabolism. Our results indicate that Activin and BMP signaling interact with the D. melanogaster metabolic response to H. bacteriophora infection regardless of the presence or absence of Photorhabdus. These findings provide evidence for the role of TGF-β signaling in host metabolism, which could lead to the development of novel treatments for parasitic diseases.

scholarly journals Chronobiotics KL001 and KS15 Extend Lifespan and Modify Circadian Rhythms of Drosophila melanogaster

2021 ◽  
Author(s):  
Ilya Solovev ◽  
Mikhail Shaposhnikov ◽  
Alexey Moskalev
Keyword(s):  
Drosophila Melanogaster ◽  
Locomotor Activity ◽  
Circadian Rhythms ◽  
Molecular Mechanisms ◽  
Fat Body ◽  
Young Male ◽  
Constant Darkness ◽  
Starvation Resistance ◽  
Positive Effects ◽  
Median Lifespan

Chronobiotics is a group of drugs utilized to modify circadian rhythms targeting clock-associated molecular mechanisms. The circadian clock is known as a controller of numerous processes standing behind aging. Hypothesis: KL001 and KS15 targeting CRY, affect lifespan, locomotor activity and circadian rhythm of Drosophila melanogaster. We observed a slight (2%, p&lt;0.001) geroprotective effect on median lifespan (5 &micro;M solution of KL001 in 0.1% DMSO) and a 14% increase in maximum lifespan in the same group. KS15 10 &micro;M solution extended males&rsquo; median lifespan by 8% (p &lt;0.05). The statistically significant positive effects of KL001 and KS15 on lifespan were not observed in female flies. KL001 5 &micro;M solution improved locomotor activity in young male imagos (p&lt;0.05) and elevated morning activity peak in aged imagos and modified robustness of circadian rhythms, leaving the period intact. KS15 10 &micro;M solution decreased the locomotor activity in constant darkness and minimized the number of rhythmic flies. KL001 5 &micro;M solution improved by 9% the mean starvation resistance in male flies (p&lt;0.01), while median resistance was elevated by 50% (p&lt;0.0001). This phenomenon may suggest the presence of the mechanism associated with improvement of fat body glucose depos&rsquo; utilization in starvation conditions which is activated by dCRY binding KL001.

scholarly journals Meep, a Novel Regulator of Insulin Signaling, Supports Development and Insulin Sensitivity via Maintenance of Protein Homeostasis in Drosophila melanogaster

2020 ◽  
Vol 10 (12) ◽  
pp. 4399-4410
Author(s):  
Matthew T. Pereira ◽  
Katia Brock ◽  
Laura Palanker Musselman
Keyword(s):  
Drosophila Melanogaster ◽  
Insulin Sensitivity ◽  
Insulin Signaling ◽  
Fat Body ◽  
Control Diet ◽  
Critical Role ◽  
Model Organism ◽  
Protein Homeostasis ◽  
Insulin Resistant ◽  
Developmental Growth

Insulin signaling is critical for developmental growth and adult homeostasis, yet the downstream regulators of this signaling pathway are not completely understood. Using the model organism Drosophila melanogaster, we took a genomic approach to identify novel mediators of insulin signaling. These studies led to the identification of Meep, encoded by the gene CG32335. Expression of this gene is both insulin receptor- and diet-dependent. We found that Meep was specifically required in the developing fat body to tolerate a high-sugar diet (HSD). Meep is not essential on a control diet, but when reared on an HSD, knockdown of meep causes hyperglycemia, reduced growth, developmental delay, pupal lethality, and reduced longevity. These phenotypes stem in part from Meep’s role in promoting insulin sensitivity and protein stability. This work suggests a critical role for protein homeostasis in development during overnutrition. Because Meep is conserved and obesity-associated in mammals, future studies on Meep may help to understand the role of proteostasis in insulin-resistant type 2 diabetes.

scholarly journals Cinnamaldehyde Improves Lifespan and Healthspan in Drosophila melanogaster Models for Alzheimer’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Hanh M. Pham ◽  
Anna Xu ◽  
Samuel E. Schriner ◽  
Evgueni A. Sevrioukov ◽  
Mahtab Jafari
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drosophila Melanogaster ◽  
Short Term Memory ◽  
Positive Impact ◽  
Fruit Fly ◽  
Cinnamon Extract ◽  
Positive Effects ◽  
Climbing Ability ◽  
The Impact

Cinnamon extract has been reported to have positive effects in fruit fly and mouse models for Alzheimer’s disease (AD). However, cinnamon contains numerous potential active compounds that have not been individually evaluated. The main objective of this study was to evaluate the impact of cinnamaldehyde, a known putative active compound in cinnamon, on the lifespan and healthspan of Drosophila melanogaster models for Alzheimer’s disease, which overexpress Aβ42 and MAPT (Tau). We found that cinnamaldehyde significantly improved the lifespan of both AD and non-AD flies. Cinnamaldehyde also improved the healthspan of AD flies overexpressing the Tau protein by improving climbing ability, evaluated by rapid iterative negative geotaxis (RING), and improving short-term memory, evaluated by a courtship conditioning assay. Cinnamaldehyde had no positive impact on the healthspan of AD flies overexpressing the Aβ42 protein.

Apoptosis and development

2003 ◽  
Vol 39 ◽  
pp. 11-24 ◽  
Author(s):  
Justin V McCarthy
Keyword(s):  
Drosophila Melanogaster ◽  
Mammalian Cells ◽  
Cell Number ◽  
Model Organisms ◽  
Biological Processes ◽  
Nematode Caenorhabditis Elegans ◽  
Apoptotic Pathway ◽  
Genetic Pathways ◽  
Evolutionarily Conserved ◽  
Multicellular Organisms

Apoptosis is an evolutionarily conserved process used by multicellular organisms to developmentally regulate cell number or to eliminate cells that are potentially detrimental to the organism. The large diversity of regulators of apoptosis in mammalian cells and their numerous interactions complicate the analysis of their individual functions, particularly in development. The remarkable conservation of apoptotic mechanisms across species has allowed the genetic pathways of apoptosis determined in lower species, such as the nematode Caenorhabditis elegans and the fruitfly Drosophila melanogaster, to act as models for understanding the biology of apoptosis in mammalian cells. Though many components of the apoptotic pathway are conserved between species, the use of additional model organisms has revealed several important differences and supports the use of model organisms in deciphering complex biological processes such as apoptosis.

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