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1.
Nat Commun ; 11(1): 4653, 2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938923

RESUMO

Cancer cells demand excess nutrients to support their proliferation, but how tumours exploit extracellular amino acids during systemic metabolic perturbations remain incompletely understood. Here, we use a Drosophila model of high-sugar diet (HSD)-enhanced tumourigenesis to uncover a systemic host-tumour metabolic circuit that supports tumour growth. We demonstrate coordinate induction of systemic muscle wasting with tumour-autonomous Yorkie-mediated SLC36-family amino acid transporter expression as a proline-scavenging programme to drive tumourigenesis. We identify Indole-3-propionic acid as an optimal amino acid derivative to rationally target the proline-dependency of tumour growth. Insights from this whole-animal Drosophila model provide a powerful approach towards the identification and therapeutic exploitation of the amino acid vulnerabilities of tumourigenesis in the context of a perturbed systemic metabolic network.


Assuntos
Açúcares da Dieta/efeitos adversos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiopatologia , Neoplasias Experimentais/fisiopatologia , Prolina/metabolismo , Sistemas de Transporte de Aminoácidos/genética , Sistemas de Transporte de Aminoácidos/metabolismo , Animais , Animais Geneticamente Modificados , Carcinogênese , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Perfilação da Expressão Gênica , Hemolinfa/efeitos dos fármacos , Hemolinfa/metabolismo , Larva , Debilidade Muscular/induzido quimicamente , Debilidade Muscular/patologia , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/patologia , Neoplasias Experimentais/etiologia , Proteínas Nucleares/genética , Receptores Proteína Tirosina Quinases/metabolismo , Transativadores/genética , Proteínas de Sinalização YAP , Proteínas ras/genética
2.
Ecotoxicol Environ Saf ; 202: 110918, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32800253

RESUMO

This work evaluates different generations of transgenic (cp4-EPSPS gene) and non-transgenic soybean plants through proteomics and metabolomics. For proteomics purpose, 24 differentially abundant protein spots were found through 2-D DIGE, being 4 belonging to transgenic plants. From this total, 19 were successfully identified, storage proteins as predominant class. Some identified proteins are involved in growing and cell division, and stress response, such as LEA and dehydrin. For metabolomics, 17 compounds were putatively annotated, mainly belonging to the secondary metabolism, such as flavonoids. From these analyzes, all generations and varieties of the soybean are prone to be differentiate by PLS-DA. According to our results, transgenic plants appear to be more stable than non-transgenic ones. In addition, the omics-based approaches allowed access some relations between those differential spot proteins and metabolites, mainly those storage proteins and flavonoid.


Assuntos
Glycine max/fisiologia , Plantas Geneticamente Modificadas/fisiologia , Metabolômica , Plantas Geneticamente Modificadas/metabolismo , Proteômica , Sementes/metabolismo , Glycine max/genética , Glycine max/metabolismo
3.
Cell Metab ; 31(4): 710-725.e7, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32197072

RESUMO

High-sugar diets cause thirst, obesity, and metabolic dysregulation, leading to diseases including type 2 diabetes and shortened lifespan. However, the impact of obesity and water imbalance on health and survival is complex and difficult to disentangle. Here, we show that high sugar induces dehydration in adult Drosophila, and water supplementation fully rescues their lifespan. Conversely, the metabolic defects are water-independent, showing uncoupling between sugar-induced obesity and insulin resistance with reduced survival in vivo. High-sugar diets promote accumulation of uric acid, an end-product of purine catabolism, and the formation of renal stones, a process aggravated by dehydration and physiological acidification. Importantly, regulating uric acid production impacts on lifespan in a water-dependent manner. Furthermore, metabolomics analysis in a human cohort reveals that dietary sugar intake strongly predicts circulating purine levels. Our model explains the pathophysiology of high-sugar diets independently of obesity and insulin resistance and highlights purine metabolism as a pro-longevity target.


Assuntos
Desidratação/induzido quimicamente , Obesidade/induzido quimicamente , Açúcares/efeitos adversos , Água/metabolismo , Animais , Drosophila/fisiologia , Humanos , Resistência à Insulina , Longevidade
4.
Cell ; 178(4): 901-918.e16, 2019 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-31398343

RESUMO

Physiology and metabolism are often sexually dimorphic, but the underlying mechanisms remain incompletely understood. Here, we use the intestine of Drosophila melanogaster to investigate how gut-derived signals contribute to sex differences in whole-body physiology. We find that carbohydrate handling is male-biased in a specific portion of the intestine. In contrast to known sexual dimorphisms in invertebrates, the sex differences in intestinal carbohydrate metabolism are extrinsically controlled by the adjacent male gonad, which activates JAK-STAT signaling in enterocytes within this intestinal portion. Sex reversal experiments establish roles for this male-biased intestinal metabolic state in controlling food intake and sperm production through gut-derived citrate. Our work uncovers a male gonad-gut axis coupling diet and sperm production, revealing that metabolic communication across organs is physiologically important. The instructive role of citrate in inter-organ communication might be significant in more biological contexts than previously recognized.


Assuntos
Metabolismo dos Carboidratos/fisiologia , Drosophila melanogaster/metabolismo , Ingestão de Alimentos/fisiologia , Mucosa Intestinal/metabolismo , Caracteres Sexuais , Maturação do Esperma/fisiologia , Animais , Ácido Cítrico/metabolismo , Proteínas de Drosophila/metabolismo , Feminino , Expressão Gênica , Janus Quinases/metabolismo , Masculino , RNA-Seq , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais , Açúcares/metabolismo , Testículo/metabolismo
5.
Funct Integr Genomics ; 19(1): 151-169, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30196429

RESUMO

Coffea arabica L. is an important agricultural commodity, accounting for 60% of traded coffee worldwide. Nitrogen (N) is a macronutrient that is usually limiting to plant yield; however, molecular mechanisms of plant acclimation to N limitation remain largely unknown in tropical woody crops. In this study, we investigated the transcriptome of coffee roots under N starvation, analyzing poly-A+ libraries and small RNAs. We also evaluated the concentration of selected amino acids and N-source preferences in roots. Ammonium was preferentially taken up over nitrate, and asparagine and glutamate were the most abundant amino acids observed in coffee roots. We obtained 34,654 assembled contigs by mRNA sequencing, and validated the transcriptional profile of 12 genes by RT-qPCR. Illumina small RNA sequencing yielded 8,524,332 non-redundant reads, resulting in the identification of 86 microRNA families targeting 253 genes. The transcriptional pattern of eight miRNA families was also validated. To our knowledge, this is the first catalog of differentially regulated amino acids, N sources, mRNAs, and sRNAs in Arabica coffee roots.


Assuntos
Coffea/genética , MicroRNAs/genética , Nitrogênio/deficiência , RNA Mensageiro/genética , RNA de Plantas/genética , Pequeno RNA não Traduzido/genética , Aminoácidos/isolamento & purificação , Aminoácidos/metabolismo , Compostos de Amônio/metabolismo , Coffea/metabolismo , Regulação da Expressão Gênica de Plantas , Ontologia Genética , Sequenciamento de Nucleotídeos em Larga Escala , MicroRNAs/classificação , MicroRNAs/metabolismo , Anotação de Sequência Molecular , Nitratos/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Poli A/genética , Poli A/metabolismo , RNA Mensageiro/classificação , RNA Mensageiro/metabolismo , RNA de Plantas/classificação , RNA de Plantas/metabolismo , Pequeno RNA não Traduzido/classificação , Pequeno RNA não Traduzido/metabolismo , Sementes/genética , Sementes/metabolismo , Estresse Fisiológico , Transcriptoma
6.
Funct Integr Genomics ; 19(1): p. 151-169, 2019.
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: but-ib15784

RESUMO

Coffea arabica L. is an important agricultural commodity, accounting for 60% of traded coffee worldwide. Nitrogen (N) is a macronutrient that is usually limiting to plant yield; however, molecular mechanisms of plant acclimation to N limitation remain largely unknown in tropical woody crops. In this study, we investigated the transcriptome of coffee roots under N starvation, analyzing poly-A+ libraries and small RNAs. We also evaluated the concentration of selected amino acids and N-source preferences in roots. Ammonium was preferentially taken up over nitrate, and asparagine and glutamate were the most abundant amino acids observed in coffee roots. We obtained 34,654 assembled contigs by mRNA sequencing, and validated the transcriptional profile of 12 genes by RT-qPCR. Illumina small RNA sequencing yielded 8,524,332 non-redundant reads, resulting in the identification of 86 microRNA families targeting 253 genes. The transcriptional pattern of eight miRNA families was also validated. To our knowledge, this is the first catalog of differentially regulated amino acids, N sources, mRNAs, and sRNAs in Arabica coffee roots.

7.
Funct Integr Genomics, v. 19, n. 1, p.151-169, jan. 2019
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-2649

RESUMO

Coffea arabica L. is an important agricultural commodity, accounting for 60% of traded coffee worldwide. Nitrogen (N) is a macronutrient that is usually limiting to plant yield; however, molecular mechanisms of plant acclimation to N limitation remain largely unknown in tropical woody crops. In this study, we investigated the transcriptome of coffee roots under N starvation, analyzing poly-A+ libraries and small RNAs. We also evaluated the concentration of selected amino acids and N-source preferences in roots. Ammonium was preferentially taken up over nitrate, and asparagine and glutamate were the most abundant amino acids observed in coffee roots. We obtained 34,654 assembled contigs by mRNA sequencing, and validated the transcriptional profile of 12 genes by RT-qPCR. Illumina small RNA sequencing yielded 8,524,332 non-redundant reads, resulting in the identification of 86 microRNA families targeting 253 genes. The transcriptional pattern of eight miRNA families was also validated. To our knowledge, this is the first catalog of differentially regulated amino acids, N sources, mRNAs, and sRNAs in Arabica coffee roots.

8.
J Plant Physiol ; 223: 9-18, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29433084

RESUMO

Under field conditions, plants are exposed to cycles of dehydration and rehydration during their lifespan. In this study, we hypothesized that sugarcane plants previously exposed to cycles of water deficits will perform better than plants that have never faced water deficits when both are subjected to low water availability. Sugarcane plants were grown in a nutrient solution and exposed to one (1WD), two (2WD) or three (3WD) water deficit cycles. As the reference, plants were grown in a nutrient solution without adding polyethylene glycol. Under water deficits, leaf gas exchange was significantly reduced in 1WD and 2WD plants. However, 3WD plants showed similar CO2 assimilation and lower stomatal conductance compared to the reference plants, with increases in intrinsic water-use efficiency. Abscisic acid concentrations were lower in 3WD plants than in 1WD plants. Our data revealed root H2O2 concentration as an important chemical signal, with the highest root H2O2 concentrations found in 3WD plants. These plants presented higher root dry matter and root:shoot ratios compared to the reference plants, as well as higher biomass production when water was available. Our data suggest that sugarcane plants were able to store information from previous stressful events, with plant performance improving under water deficits. In addition, our findings provide a new perspective for increasing drought tolerance in sugarcane plants under nursery conditions.


Assuntos
Secas , Saccharum/fisiologia , Água/metabolismo , Ácido Abscísico/metabolismo , Peróxido de Hidrogênio/metabolismo , Folhas de Planta/anatomia & histologia , Folhas de Planta/química , Folhas de Planta/fisiologia , Raízes de Plantas/fisiologia , Saccharum/anatomia & histologia , Saccharum/química , Transdução de Sinais/fisiologia
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