Cucurbitacin B Suppresses Hyperglycemia Associated with a High Sugar Diet and Promotes Sleep in Drosophila melanogaster

Obesity and its comorbidities are a growing health epidemic. Interactions between genetic background, the environment, and behavior (i.e., diet) greatly influence organismal energy balance. Previously, we described obesogenic mutations in the gene Split ends (Spen) in Drosophila melanogaster, and roles for Spen in fat storage and metabolic state. Lipid catabolism is impaired in Spen-deficient fat storage cells, accompanied by a compensatory increase in glycolytic flux and protein catabolism. Here, we investigate gene–diet interactions to determine if diets supplemented with specific macronutrients can rescue metabolic dysfunction in Spen-depleted animals. We show that a high-yeast diet partially rescues adiposity and developmental defects. High sugar partially improves developmental timing as well as longevity of mated females. Gene–diet interactions were heavily influenced by developmental-stage-specific organismal needs: extra yeast provides benefits early in development (larval stages) but becomes detrimental in adulthood. High sugar confers benefits to Spen-depleted animals at both larval and adult stages, with the caveat of increased adiposity. A high-fat diet is detrimental according to all tested criteria, regardless of genotype. Whereas Spen depletion influenced phenotypic responses to supplemented diets, diet was the dominant factor in directing the whole-organism steady-state metabolome. Obesity is a complex disease of genetic, environmental, and behavioral inputs. Our results show that diet customization can ameliorate metabolic dysfunction underpinned by a genetic factor.

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RNA-Sequencing of Drosophila melanogaster Head Tissue on High-Sugar and High-Fat Diets

G3 Genes|Genome|Genetics ◽

10.1534/g3.117.300397 ◽

2017 ◽

Vol 8 (1) ◽

pp. 279-290 ◽

Cited By ~ 9

Author(s):

Wayne Hemphill ◽

Osvaldo Rivera ◽

Matthew Talbert

Keyword(s):

Drosophila Melanogaster ◽

Rna Sequencing ◽

High Fat ◽

High Sugar ◽

High Fat Diets ◽

Fat Diets

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Solanum anguivi Lam. fruit preparations counteract the negative effects of a high-sugar diet on the glucose metabolism in Drosophila melanogaster

Food & Function ◽

10.1039/d1fo01363g ◽

2021 ◽

Author(s):

Aisha Musaazi Sebunya Nakitto ◽

Silvia Rudloff ◽

Christian Borsch ◽

Anika Wagner

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Drosophila Melanogaster ◽

Glucose Metabolism ◽

Negative Effects ◽

High Sugar ◽

Underlying Mechanisms

Solanum anguivi Lam. fruits (SALF) are traditionally consumed as a remedy for type 2 diabetes mellitus (T2DM). However, data regarding the potential anti-diabetic effect of SALF and its underlying mechanisms...

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Domeless receptor loss in fat body tissue reverts insulin resistance induced by a high-sugar diet in Drosophila melanogaster

Scientific Reports ◽

10.1038/s41598-021-82944-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Fernanda Lourido ◽

Daniela Quenti ◽

Daniela Salgado-Canales ◽

Nicolás Tobar

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Drosophila Melanogaster ◽

Metabolic Response ◽

Fat Body ◽

High Sugar ◽

Diabetes Model ◽

Inflammatory Processes ◽

Stat Pathway

AbstractInsulin resistance is a hallmark of type 2 diabetes resulting from the confluence of several factors, including genetic susceptibility, inflammation, and diet. Under this pathophysiological condition, the dysfunction of the adipose tissue triggered by the excess caloric supply promotes the loss of sensitivity to insulin at the local and peripheral level, a process in which different signaling pathways are involved that are part of the metabolic response to the diet. Besides, the dysregulation of insulin signaling is strongly associated with inflammatory processes in which the JAK/STAT pathway plays a central role. To better understand the role of JAK/STAT signaling in the development of insulin resistance, we used a simple organism, Drosophila melanogaster, as a type 2 diabetes model generated by the consumption of a high-sugar diet. In this model, we studied the effects of inhibiting the expression of the JAK/STAT pathway receptor Domeless, in fat body, on adipose metabolism and glycemic control. Our results show that the Domeless receptor loss in fat body cells reverses both hyperglycemia and the increase in the expression of the insulin resistance marker Nlaz, observed in larvae fed a high sugar diet. This effect is consistent with a significant reduction in Dilp2 mRNA expression and an increase in body weight compared to wild-type flies fed high sugar diets. Additionally, the loss of Domeless reduced the accumulation of triglycerides in the fat body cells of larvae fed HSD and also significantly increased the lifespan of adult flies. Taken together, our results show that the loss of Domeless in the fat body reverses at least in part the dysmetabolism induced by a high sugar diet in a Drosophila type 2 diabetes model.

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Bilberry (Vaccinium myrtillus L.) Extracts Comparative Analysis Regarding Their Phytonutrient Profiles, Antioxidant Capacity along with the In Vivo Rescue Effects Tested on a Drosophila melanogaster High-Sugar Diet Model

Antioxidants ◽

10.3390/antiox9111067 ◽

2020 ◽

Vol 9 (11) ◽

pp. 1067 ◽

Cited By ~ 1

Author(s):

Andreea-Adriana Neamtu ◽

Rita Szoke-Kovacs ◽

Emoke Mihok ◽

Cecilia Georgescu ◽

Violeta Turcus ◽

...

Keyword(s):

Antioxidant Activity ◽

Drosophila Melanogaster ◽

Total Content ◽

Vaccinium Myrtillus ◽

Anthocyanin Content ◽

Fruit Extract ◽

High Sugar ◽

Bilberry Extract ◽

Vaccinium Myrtillus L

Bilberries (Vaccinium myrtillus L.) have been reported to hold a plentitude of health-promoting properties beyond basic nutrition, mainly attributed to their anthocyanin content and antioxidant activity. In this article, we built the phytochemical profile of three wild bilberry fruit extract formulations (aqueous, methanolic, and hydro-methanolic) using UHPLC-ESI-MS/MS putative analysis, identifying 88 individual phytochemicals, mainly flavonoids (total content 8.41 ± 0.11 mg QE/g dw), free amino acids, polyphenols (total content 21.68 ± 0.19 mg GAE/g dw), carboxylic acids, and vitamins. Furthermore, the antioxidant activity of the extract was assessed, reaching 78.03 ± 0.16% DPPH free radical scavenging activity, comparable to literature values determined for bilberry extracts of other origin. Due to the increased prevalence of metabolic syndrome and based on the reviewed benefits of bilberries, we tested the most potent formulation of our bilberry extracts in this biological context. The in vivo rescue effect of a bilberry extract supplemented diet on Drosophila melanogaster was assessed by monitoring biochemical and genomic markers. Hemolymph trehalose levels were halved upon addition of 3% hydro-methanolic bilberry extract to a high-sugar (1.5 M sucrose) diet, as compared to the non-supplemented high-sugar diet. Noteworthy, the rescue seen for flies kept on the bilberry extract supplemented high-sugar diet appeared to parallel the trehalose levels observed in the case of the control diet (50 mM sucrose) flies. Moreover, next to the trehalose-lowering type of in vivo effects, other gene expression related rescues were also detected for genes such as InR, Akh, AstA, AstC, Irk, Npc2g, and CCHa2 upon supplementation of the high-sugar diet with our hydro-methanolic bilberry fruit extract. Our findings suggest that such a bilberry fruit extract could generate physiological and genomic type of compensatory mechanisms so that further translational approaches would advance the understanding of some human specific pathological conditions.

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Symbiotic bacterial community of Drosophila melanogaster changes with nutritional modifications of the diet but can alleviate negative effects on larval phenotypes

10.1101/2021.09.07.458894 ◽

2021 ◽

Author(s):

Andrei Bombin ◽

Owen Cunneely ◽

Sergei Bombin ◽

Kira Eickman ◽

Abigail Ruesy ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Bacterial Communities ◽

Metabolic Phenotype ◽

Model Organisms ◽

Human Populations ◽

High Fat ◽

Negative Effects ◽

High Sugar ◽

Dominant Bacteria ◽

Dietary Modifications

ABSTRACTObesity is an increasing pandemic and is caused by multiple factors including genotype, psychological stress, and gut microbiota. Our project investigated the effects produced by high fat and high sugar dietary modifications on microbiota and metabolic phenotype of Drosophila melanogaster. Larvae raised on the high fat and high sugar diets exhibited bacterial communities that were compositionally and phylogenetically different from bacterial communities of the larvae raised on normal diets, especially if parental microbiota were removed. Several of the dominant bacteria taxa that are commonly associated with high fat and high sugar diets across model organisms and even human populations showed similar pattern in our results. Corynebacteriaceae and Erysipelotrichaceae were connected with high fat food, while Enterobacteriaceae and Lactobacillaceae were associated with high sugar diets. In addition, we observed that presence of symbiotic microbiota often mitigated the effect that harmful dietary modifications produced on larvae, including elevated triglyceride concentrations and was crucial for Drosophila survival, especially on high sugar peach diets.

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Larval mannitol diets increase mortality, prolong development, and decrease adult body sizes in fruit flies (Drosophila melanogaster)

10.1101/674192 ◽

2019 ◽

Author(s):

Meghan Barrett ◽

Katherine Fiocca ◽

Edward A. Waddell ◽

Cheyenne McNair ◽

Sean O’Donnell ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Larval Mortality ◽

Larval Survival ◽

Offspring Performance ◽

The Third ◽

High Sugar ◽

Developmental Effects ◽

Adult Body ◽

Body Sizes ◽

Lower Magnitude

AbstractIngestion of the polyol mannitol caused sex-biased mortality in adultDrosophila melanogaster, but larval mortality was not sex-biased. High-sugar diets prolong development and generate smaller adult body sizes inD. melanogaster. We hypothesized that mannitol ingestion would generate similar developmental phenotypes as other high-carbohydrate diets. We predicted concentration-dependent effects on development similar to high-sugar diets whenD. melanogasterlarvae are fed mannitol, as well as a concentration-dependent amelioration of developmental effects if introduction to mannitol media is delayed past the third instar. Both male and female larvae had prolonged development and smaller adult body sizes when fed increasing concentrations of mannitol. Mannitol-induced increases in mortality were concentration dependent in 0 M to 0.8 M treatments beginning as early as 48 hours post-hatching. Larval survival, and pupation and eclosion times, were normal in 0.4 M mannitol treatments when larvae were first introduced to mannitol 72 hours post-hatching (the beginning of the third-instar); the adverse mannitol effects occurred in 0.8 M mannitol treatments, but at a lower magnitude. FemaleD. melanogasteradults prefer laying eggs on diets with high sugar concentrations, despite the negative effects on offspring performance. However, when given a choice, femaleD. melanogasteravoided laying eggs on mannitol-containing media that was otherwise identical to the control media, suggesting females perceived and avoided mannitol. In conclusion, the developmental effects of a larval mannitol diet closely resemble those of high-sugar diets, but adult female oviposition responses to mannitol in laying substrates are distinct from responses to other carbohydrates.

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