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Influences of Bwoman-Birk Inhibitor on genomics in Drosophila melanogaster larval midguts

ABSTRACT: Bowman-Birk Inhibitor (BBI) has both insecticidal and anti-cancerous properties. It has been hypothesized that dietary BBI slows insect growth by inhibiting the catalytic activity of digestive enzymes trypsins and chyomotrypsins, resulting in the midgut having reduced access to amino acids needed for growth. In mammals, BBI was hypothesized to influence cellular energy metabolism. Thus, we tested the hypothesis that dietary BBI also impacts energy-associated pathways in the midgut of Drosophila melanogaster. We investigated the impact of dietary BBI on the following parameters in the midguts of third-instar Drosophila larvae: (i) cellular metabolites, (ii) global transcriptome response, (iii) putative transcription factor binding sites (TFBSs) associated with the differentially expressed transcripts, and (iv) epithelial cellular structure. Dietary BBI caused: (i) a reduction of cellular DHAP, glucose, and succinate; and, (ii) increased Fructuse-6-phosphate; (ii) differential expression of genes associated with the glucose and fatty acid utilization; and, (iii) a shortening of midgut epithelial microvilli, a phenomenon previously associated with glucose starvation. Additionally, fifty seven percent of the putative TFBSs associated with the differentially expressed transcripts have previously been associated with glucose and insulin activities in mammalian studies. Collectively these results support the hypothesis that dietary BBI influences energy utilization in the Drosophila midgut. Keywords: stress response

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE11046 | GEO | 2008/10/03

SECONDARY ACCESSION(S): PRJNA107029

REPOSITORIES: GEO

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Influences of Bowman-Birk Inhibitor on genomics in Drosophila melanogaster larval midguts

Project description:Bowman-Birk Inhibitor (BBI) has both insecticidal and anti-cancerous properties. It has been hypothesized that dietary BBI slows insect growth by inhibiting the catalytic activity of digestive enzymes trypsins and chyomotrypsins, resulting in the midgut having reduced access to amino acids needed for growth. In mammals, BBI was hypothesized to influence cellular energy metabolism. Thus, we tested the hypothesis that dietary BBI also impacts energy-associated pathways in the midgut of Drosophila melanogaster. We investigated the impact of dietary BBI on the following parameters in the midguts of third-instar Drosophila larvae: (i) cellular metabolites, (ii) global transcriptome response, (iii) putative transcription factor binding sites (TFBSs) associated with the differentially expressed transcripts, and (iv) epithelial cellular structure. Dietary BBI caused: (i) a reduction of cellular DHAP, glucose, and succinate; and, (ii) increased Fructuse-6-phosphate; (ii) differential expression of genes associated with the glucose and fatty acid utilization; and, (iii) a shortening of midgut epithelial microvilli, a phenomenon previously associated with glucose starvation. Additionally, fifty seven percent of the putative TFBSs associated with the differentially expressed transcripts have previously been associated with glucose and insulin activities in mammalian studies. Collectively these results support the hypothesis that dietary BBI influences energy utilization in the Drosophila midgut. Experiment Overall Design: Two treatments (control vs BBI-fed), and three replicates were conducted. There were total six samples. There was no dye-swap.

2008-10-26 | E-GEOD-11046 | biostudies-arrayexpress

Transcriptional Signatures in Response to Wheat Germ Agglutinin and Starvation in Drosophila melanogaster Larval Midgut

Project description:One function of plant lectins is to serve as defenses against herbivorous insects. The midgut is the critical site affected by dietary lectins such as wheat germ agglutinin (WGA). We observed marked cellular structural and gene expression changes in Drosophila melanogaster third-instar larval midguts from insects WGA-fed or starved. Dietary WGA caused shortening, branching, swelling, distortion and in some cases disintegration of the midgut microvilli (Mv). Starvation was accompanied by shortening of the Mv. Microarray analyses revealed that dietary WGA evolved differential expression of 62 transcripts; seven of which were also differentially expressed in starved insects. The differentially regulated gene cluster in WGA-fed larvae were associated with (i) cytoskeletal organization, (ii) immune responses, (iii) detoxification reactions, and (iv) energy metabolism. Four putative transcription factor binding motifs (TFBMs) were associated with the differentially-expressed genes. At least one of these putative TFBMs exhibited substantial similarity to MyoD, a TFBM associated with cellular structures in mammals. These results are in keeping with the hypothesis that WGA causes a starvation-like effect as well as structural changes of midgut cells of Drosophila third-instar larvae. Experiment Overall Design: Three treatments (control, WGA, and Starvation), and three replicates for each treatment. So there are total nine samples. no dye-swap.

2008-10-26 | E-GEOD-11047 | biostudies-arrayexpress

Transcriptional Signatures in Response to Wheat Germ Agglutinin and Starvation in Drosophila melanogaster Larval Midgut

2008-10-03 | GSE11047 | GEO

Nutrient-driven dedifferentiation of enteroendocrine cells promotes adaptive intestinal growth

Project description:Post-developmental organ resizing improves organismal fitness under constantly changing nutrient environments. Although stem cell abundance is a fundamental determinant of adaptive resizing, our understanding of its underlying mechanisms remains primarily limited to the regulation of stem cell division. Here, we demonstrate that nutrient fluctuation induces dedifferentiation in the Drosophila adult midgut to drive adaptive intestinal growth. From lineage tracing and single-cell RNA sequencing, we identify a subpopulation of enteroendocrine (EE) cells that convert into functional intestinal stem cells (ISCs) in response to dietary glucose and amino acids by activating the JAK-STAT pathway. Genetic ablation of EE-derived ISCs severely impairs ISC expansion and midgut growth despite the retention of resident ISCs, and in silico modeling further indicates that EE dedifferentiation enables an efficient increase in the midgut cell number while maintaining epithelial cell composition. Our findings identify a physiologically induced dedifferentiation that ensures ISC expansion during adaptive organ growth in concert with nutrient conditions.

2023-08-12 | GSE207662 | GEO

Transcriptome profiling of Drosophila Wild Type and Sc overexpressed intestinal progenitor cells

Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare transcriptome profiling (RNA-seq) of intestinal progenitor cells in Drosophila wild type and Sc overexpressed midgut. Methods: mRNA profiles of intestinal progenitor cells isolated from 2-day-old wild-type (Ctrl) and Sc overexpressed(ScOE) Drosophila midgut were generated by deep sequencing using Illumina HiSeq 4000. Results:

2018-02-02 | GSE102569 | GEO

TGF β signaling functions as a sugar sensing feedback loop to regulate digestive enzyme expression.

Project description:Organisms need to assess their nutritional state and adapt their digestive capacity to the demands for various nutrients. Modulation of digestive enzyme production represents a potential step to regulate nutriment intake. However, the role of digestion in nutrient homeostasis has been largely neglected. In this study, we analyzed the mechanism underlying glucose repression of amylase in the adult Drosophila midgut. We demonstrated that glucose represses many carbohydrases and lipases. Our data shows that the consumption of nutritious sugars stimulates the secretion of the TGFβ ligand, Dawdle. Dawdle then acts via the circulation to activate TGFβ/Activin signaling in the midgut, culminating in the repression of digestive enzyme expression. Thus, our study not only identifies a mechanism coupling sugar sensing to digestive enzyme expression but points to an important role of TGFβ/Activin signaling in sugar metabolism. RNA-sequencing of whole guts from Drosophila melannogaster OregonR adult females was performed under three feeding conditions: Standard medium, glucose, and agar. Three biological repeats were performed for each condition.

2014-09-10 | E-GEOD-54755 | biostudies-arrayexpress

Drosophila E78A nuclear receptor regulates intestinal dietary triacylglyceride uptake and systemic lipid levels

Project description:Here we show that the Drosophila nuclear receptor E78A regulates transcription in adult animals facilitating dietary lipid uptake. E78A mutant adults are viable with normal developmental timing, locomotor activity, female fecundity, but have significantly reduced stored triglycerides. This reduction in whole body triglyceride stores appears to originate from the midgut, using neutral lipid stainings we determined lipid levels in the midgut were greatly reduced. Upon examining our RNA-seq analysis we found that a gastric lipase, CG17192, is transcriptionally coordinated by E78A. CG17192 is expressed in an adult, intestinal specific fashion within control flies, and has a human ortholog. Through dietary supplementation and genetic testing we determined that the whole body hypolipidemia seen within E78A mutants is dependent on CG17192 expression within the intestine. Restoration of this lipase in the intestine of mutant flies is sufficient to restore normal lipid levels. Our data support the model that E78A contributes to a transcriptional regulation of the gastric lipase, CG17192, thus directing dietary triglyceride uptake in the adult fly.

2021-01-01 | GSE152031 | GEO

Stem cell intrinsic nutrient sensing regulating diet dependent intestinal adaptation

Project description:The intestine is an organ with exceptionally high rate of cell turnover and perturbations in this process can lead to disease such as cancer or intestinal atrophy. Nutrition is a key factor regulating the intestinal cell turnover and has a profound impact on intestinal volume and cellular architecture. However, how the intestinal equilibrium is maintained in fluctuating dietary conditions is insufficiently understood. By utilizing the Drosophila midgut as a model, we reveal a novel nutrient sensing mechanism coupling stem cell metabolism with stem cell extrinsic growth signal. Our results show that intestinal stem cells (ISCs) employ the hexosamine biosynthesis pathway (HBP) to monitor nutritional status and energy metabolism. Elevated activity of the HBP promotes Warburg effect-like metabolic reprogramming, which is required for the reactivation of ISCs from calorie restriction-induced quiescence. Furthermore, the HBP activity is an essential facilitator for insulin signaling-induced intestinal growth. In conclusion, intestinal stem cell intrinsic nutrient sensing regulates metabolic pathway activities, and defines the stem cell responsiveness to niche-derived growth signals.

2018-09-13 | GSE107052 | GEO

The role of dietary leucine and dairy protein on hepatic gene expression

Project description:We used microarray to determine the differences in hepatic gene expression for diet-induced obese Sprague-Dawley rats consuming different dietary proteins. Proteins of interest included skim milk powder (dairy), casein, and the branched-chain amino acid, leucine. The primary aims of this study were: (i) to compare the effects of diets with protein derived from casein, casein supplemented with leucine, and complete dairy on body composition and insulin sensitivity; and (ii) to determine if there is a synergistic effect of dietary Ca and protein source on body composition and insulin sensitivity. Secondarily, we used microarray analysis to examine the effect of casein, leucine, or complete dairy containing diets on the expression of hepatic genes related to lipid and glucose metabolism. Diet induced obese rats consumed ad libitum, a high fat, high sucrose diet for 8 weeks (n=4). All diets had an energy density of 4.6 kcal/gram and provided 10% of total energy from protein [casein, complete dairy (skim milk powder), or leucine-supplemented casein (7.1% from casein plus 2.9% from leucine)]. The casein treatment was the control diet.

2010-08-12 | E-GEOD-23559 | biostudies-arrayexpress

The role of dietary leucine and dairy protein on gastrocemius muscle gene expression

Project description:We used microarray to determine the differences in hepatic gene expression for diet-induced obese Sprague-Dawley rats consuming different dietary proteins. Proteins of interest included skim milk powder (dairy), casein, and the branched-chain amino acid, leucine. The primary aims of this study were: (i) to compare the effects of diets with protein derived from casein, casein supplemented with leucine, and complete dairy on body composition and insulin sensitivity; and (ii) to determine if there is a synergistic effect of dietary Ca and protein source on body composition and insulin sensitivity. Secondarily, we used microarray analysis to examine the effect of casein, leucine, or complete dairy containing diets on the expression of gastrocnemius muscle genes related to lipid and glucose metabolism. Diet induced obese rats consumed ad libitum, a high fat, high sucrose diet for 8 weeks (n=4). All diets had an energy density of 4.6 kcal/gram and provided 10% of total energy from protein [casein, complete dairy (skim milk powder), or leucine-supplemented casein (7.1% from casein plus 2.9% from leucine)]. The casein treatment was the control diet.

2011-10-21 | E-GEOD-33144 | biostudies-arrayexpress

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