A Comparison of the Metabolome of Male and Female Drosophila melanogaster

Zhang, Rong; Zhang, Tong; Korzekwa, Dominika; Al-Johani, Shadi; Dow, Julian A. T.; Watson, David

doi:10.2174/2213235x03666150108233830

Cited by 5 publications

(10 citation statements)

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“…Further, metabolomics methodologies are more recently also applied to Drosophila 60 – 63 and allow for a more global survey of metabolites, which will allow even more fine-grained analyses and deeper insights. Using metabolomics, for example, the differential metabolic repertoire of female and male flies as suggested by gene expression analyses 64 could be confirmed 65 , 66 . One of the studies revealed that females show a higher proportion of acylated amino acids, which might be associated with the microbiome based on their enrichment in the gut 65 .…”

Section: Discussionmentioning

confidence: 97%

“…Using metabolomics, for example, the differential metabolic repertoire of female and male flies as suggested by gene expression analyses 64 could be confirmed 65 , 66 . One of the studies revealed that females show a higher proportion of acylated amino acids, which might be associated with the microbiome based on their enrichment in the gut 65 . Tissue specificity and a more fine-grained analysis of the interaction between the metabolic profile, the gut microbiome composition and the impact of environmental factors thus will be highly informative.…”

Section: Discussionmentioning

confidence: 97%

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The impact of genome variation and diet on the metabolic phenotype and microbiome composition of Drosophila melanogaster

Jehrke

Stewart

Droste

et al. 2018

Sci Rep

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The metabolic phenotype of an organism depends on a complex regulatory network, which integrates the plethora of intrinsic and external information and prioritizes the flow of nutrients accordingly. Given the rise of metabolic disorders including obesity, a detailed understanding of this regulatory network is in urgent need. Yet, our level of understanding is far from completeness and complicated by the discovery of additional layers in metabolic regulation, such as the impact of the microbial community present in the gut on the hosts’ energy storage levels. Here, we investigate the interplay between genome variation, diet and the gut microbiome in the shaping of a metabolic phenotype. For this purpose, we reared a set of fully sequenced wild type Drosophila melanogaster flies under basal and nutritionally challenged conditions and performed metabolic and microbiome profiling experiments. Our results introduce the fly as a model system to investigate the impact of genome variation on the metabolic response to diet alterations and reveal candidate single nucleotide polymorphisms associated with different metabolic traits, as well as metabolite-metabolite and metabolite-microbe correlations. Intriguingly, the dietary changes affected the microbiome composition less than anticipated. These results challenge the current view of a rapidly changing microbiome in response to environmental fluctuations.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 97%

The impact of genome variation and diet on the metabolic phenotype and microbiome composition of Drosophila melanogaster

Jehrke

Stewart

Droste

et al. 2018

Sci Rep

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“…Metabolomic profiling was carried out on a ZICpHILIC column (150 × 4.6 mm, 5 μm, HiChrom, Reading, UK) and an Orbitrap Exactive MS using conditions described previously [34] . Data extraction and data base searching were also carried out as described previously [34] .…”

Section: Methodsmentioning

confidence: 99%

Fenretinide mediated retinoic acid receptor signalling and inhibition of ceramide biosynthesis regulates adipogenesis, lipid accumulation, mitochondrial function and nutrient stress signalling in adipocytes and adipose tissue

Mcilroy

Tammireddy

Maskrey

et al. 2016

Biochemical Pharmacology

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Graphical abstractProposed mechanistic action of FEN in adipocytes. RA inhibits adipogenesis through early RAR activation, which PPARγ agonist ROSI cannot prevent. FEN inhibits adipogenesis with a delayed response in RAR signalling, however, inhibition is lost when combined with ROSI. The 4-OXO FEN catabolite cannot inhibit adipogenesis through RAR activation, but like FEN’s RAR-independent effects, displays increased phosphorylation of Akt, mild cellular stress/autophagy induction and decreased lipid accumulation. Moreover, FEN-mediated inhibition of DES-1 increases dihydroceramide levels in a RAR-independent manner, and is linked to a complete prevention of mitochondrial dysfunction and decreased adiposity in high-fat fed obese mice. Thus an alternative to the additive beneficial effects of FEN-mediated RAR-dependant and -independent signalling, 4-OXO FEN may be a novel therapeutic candidate to improve adipocyte hypertrophy via inhibition of ceramide biosynthesis and modulation of nutrient stress pathways.

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“…26,38,44,46,47 Furthermore, of particular relevance to the present study, the fly model is also amenable to metabolomic studies. 32,48,49 We display, for the first time, the metabolic profile of the Drosophila HD model using 1D 1 H NMR spectroscopy. We show that the cellular pool of nicotinamide adenine dinucleotide (NAD), a coenzyme involved in energy metabolism, is progressively affected with increasing severity of HD.…”

Section: ■ Introductionmentioning

confidence: 99%

“…For instance, the dpink1 loss - induced Drosophila Parkinson neurodegenerative phenotype is rescued by the overexpression of its human homologue, hPINK 1 . It is now well recognized that Drosophila HD model generated by targeted expression of expanded polyQ-repeats in the developing eye recapitulates HD pathology. ,, The severity and range of these HD phenotypes correspond to the lengths of misexpressed polyQ repeats. , These Drosophila HD pathologies include aberrant axonal transport, aggregates of polyQ-rich peptides at synapses, nonautonomous spread of aggregates to neighboring neurons along with photoreceptor, and neuronal degeneration. ,,,, Furthermore, of particular relevance to the present study, the fly model is also amenable to metabolomic studies. ,, …”

Section: Introductionmentioning

confidence: 99%

NMR Spectroscopy-based Metabolomics of Drosophila Model of Huntington’s Disease Suggests Altered Cell Energetics

et al. 2017

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Huntington's disease (HD) is a neurodegenerative disorder induced by aggregation of the pathological form of Huntingtin protein that has expanded polyglutamine (polyQ) repeats. In the Drosophila model, for instance, expression of transgenes with polyQ repeats induces HD-like pathologies, progressively correlating with the increasing lengths of these repeats. Previous studies on both animal models and clinical samples have revealed metabolite imbalances during HD progression. To further explore the physiological processes linked to metabolite imbalances during HD, we have investigated the 1D H NMR spectroscopy-based metabolomics profile of Drosophila HD model. Using multivariate analysis (PCA and PLS-DA) of metabolites obtained from methanolic extracts of fly heads displaying retinal deformations due to polyQ overexpression, we show that the metabolite imbalance during HD is likely to affect cell energetics. Six out of the 35 metabolites analyzed, namely, nicotinamide adenine dinucleotide (NAD), lactate, pyruvate, succinate, sarcosine, and acetoin, displayed segregation with progressive severity of HD. Specifically, HD progression was seen to be associated with reduction in NAD and increase in lactate-to-pyruvate ratio. Furthermore, comparative analysis of fly HD metabolome with those of mouse HD model and HD human patients revealed comparable metabolite imbalances, suggesting altered cellular energy homeostasis. These findings thus raise the possibility of therapeutic interventions for HD via modulation of cellular energetics.

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A Comparison of the Metabolome of Male and Female Drosophila melanogaster

Cited by 5 publications

References 0 publications

The impact of genome variation and diet on the metabolic phenotype and microbiome composition of Drosophila melanogaster

The impact of genome variation and diet on the metabolic phenotype and microbiome composition of Drosophila melanogaster

Fenretinide mediated retinoic acid receptor signalling and inhibition of ceramide biosynthesis regulates adipogenesis, lipid accumulation, mitochondrial function and nutrient stress signalling in adipocytes and adipose tissue

NMR Spectroscopy-based Metabolomics of Drosophila Model of Huntington’s Disease Suggests Altered Cell Energetics

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