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1.
Nat Commun ; 11(1): 4653, 2020 09 16.
Article in English | MEDLINE | ID: mdl-32938923

ABSTRACT

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.


Subject(s)
Dietary Sugars/adverse effects , Muscle, Skeletal/drug effects , Muscle, Skeletal/physiopathology , Neoplasms, Experimental/physiopathology , Proline/metabolism , Amino Acid Transport Systems/genetics , Amino Acid Transport Systems/metabolism , Animals , Animals, Genetically Modified , Carcinogenesis , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Drosophila melanogaster/genetics , Drosophila melanogaster/metabolism , Fibroblast Growth Factors/genetics , Fibroblast Growth Factors/metabolism , Gene Expression Profiling , Hemolymph/drug effects , Hemolymph/metabolism , Larva , Muscle Weakness/chemically induced , Muscle Weakness/pathology , Muscular Atrophy/chemically induced , Muscular Atrophy/pathology , Neoplasms, Experimental/etiology , Nuclear Proteins/genetics , Receptor Protein-Tyrosine Kinases/metabolism , Trans-Activators/genetics , YAP-Signaling Proteins , ras Proteins/genetics
2.
Ecotoxicol Environ Saf ; 202: 110918, 2020 Oct 01.
Article in English | MEDLINE | ID: mdl-32800253

ABSTRACT

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.


Subject(s)
Glycine max/physiology , Plants, Genetically Modified/physiology , Metabolomics , Plants, Genetically Modified/metabolism , Proteomics , Seeds/metabolism , Glycine max/genetics , Glycine max/metabolism
3.
Cell Metab ; 31(4): 710-725.e7, 2020 04 07.
Article in English | MEDLINE | ID: mdl-32197072

ABSTRACT

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.


Subject(s)
Dehydration/chemically induced , Obesity/chemically induced , Sugars/adverse effects , Water/metabolism , Animals , Drosophila/physiology , Humans , Insulin Resistance , Longevity
4.
Cell ; 178(4): 901-918.e16, 2019 08 08.
Article in English | MEDLINE | ID: mdl-31398343

ABSTRACT

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.


Subject(s)
Carbohydrate Metabolism/physiology , Drosophila melanogaster/metabolism , Eating/physiology , Intestinal Mucosa/metabolism , Sex Characteristics , Sperm Maturation/physiology , Animals , Citric Acid/metabolism , Drosophila Proteins/metabolism , Female , Gene Expression , Janus Kinases/metabolism , Male , RNA-Seq , STAT Transcription Factors/metabolism , Signal Transduction , Sugars/metabolism , Testis/metabolism
5.
Funct Integr Genomics ; 19(1): 151-169, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30196429

ABSTRACT

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.


Subject(s)
Coffea/genetics , MicroRNAs/genetics , Nitrogen/deficiency , RNA, Messenger/genetics , RNA, Plant/genetics , RNA, Small Untranslated/genetics , Amino Acids/isolation & purification , Amino Acids/metabolism , Ammonium Compounds/metabolism , Coffea/metabolism , Gene Expression Regulation, Plant , Gene Ontology , High-Throughput Nucleotide Sequencing , MicroRNAs/classification , MicroRNAs/metabolism , Molecular Sequence Annotation , Nitrates/metabolism , Plant Leaves/genetics , Plant Leaves/metabolism , Plant Roots/genetics , Plant Roots/metabolism , Poly A/genetics , Poly A/metabolism , RNA, Messenger/classification , RNA, Messenger/metabolism , RNA, Plant/classification , RNA, Plant/metabolism , RNA, Small Untranslated/classification , RNA, Small Untranslated/metabolism , Seeds/genetics , Seeds/metabolism , Stress, Physiological , Transcriptome
6.
Funct Integr Genomics, v. 19, n. 1, p.151-169, jan. 2019
Article in English | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-2649

ABSTRACT

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 ; 19(1): p. 151-169, 2019.
Article in English | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: but-ib15784

ABSTRACT

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.
Article in English | MEDLINE | ID: mdl-29433084

ABSTRACT

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.


Subject(s)
Droughts , Saccharum/physiology , Water/metabolism , Abscisic Acid/metabolism , Hydrogen Peroxide/metabolism , Plant Leaves/anatomy & histology , Plant Leaves/chemistry , Plant Leaves/physiology , Plant Roots/physiology , Saccharum/anatomy & histology , Saccharum/chemistry , Signal Transduction/physiology
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