Here we study the adult functions of the single Drosophila member of this subfamily, DHR78, with the goal of defining its ancestral functions in the absence of genetic redundancy. We show that DHR78 mutants have a shortened lifespan and reduced motility. Mated DHR78 mutant females display reduced triglycerides along with a reduced feeding rate. Transcriptional profiling reveals a major role for DHR78 in promoting the expression of genes that are abundantly expressed in the midgut, suggesting that it contributes to nutrient uptake. We also identify roles for DHR78 in maintaining the expression of genes in the ecdysone and Notch signaling pathways. Overall design: Comparison of the transcriptional profile of DHR78-transheterozygote female mutants in a btl>DHR78 background with genetically matched controls
Adult functions for the Drosophila DHR78 nuclear receptor.
Sex, Age, Specimen part, Subject
View SamplesAlthough SIRT1 plays a central role in maintaining metabolic homeostasis, the molecular mechanisms remain unclear. Here we show that loss of the Drosophila SIRT1 homolog sir2 leads to the progressive onset of diabetic phenotypes, similar to studies of SIRT1 in mice. Sir2 function is both necessary and sufficient in the fat body to maintain peripheral insulin sensitivity. This activity is mediated by the Drosophila HNF4 nuclear receptor, which is deacetylated and stabilized through protein interactions with Sir2. This study demonstrates that the key metabolic activities of SIRT1 have been conserved through evolution and establishes HNF4 as a critical downstream target. Overall design: 4 sir2 mutant, 4 control samples, independent biological replicates
Sir2 Acts through Hepatocyte Nuclear Factor 4 to maintain insulin Signaling and Metabolic Homeostasis in Drosophila.
Age, Subject
View SamplesThis study identifies genes that alter their expression in synchrony with the late third instar and prepupal pulses of 20E.
The genomic response to 20-hydroxyecdysone at the onset of Drosophila metamorphosis.
No sample metadata fields
View SamplesThis study identifies those genes that are dependent on EcR for their proper regulation at the onset of metamorphosis in Drosophila melanogaster.
The genomic response to 20-hydroxyecdysone at the onset of Drosophila metamorphosis.
No sample metadata fields
View SamplesTo identify 20E-regulated genes, wandering third instar larvae were dissected and their organs were cultured in the presence of either no hormone, 20E alone, cycloheximide alone, or 20E plus cycloheximide for six hours.
The genomic response to 20-hydroxyecdysone at the onset of Drosophila metamorphosis.
No sample metadata fields
View SamplesPhenobarbital is a well studied xenobiotic compound. In this study, we describe the genomic responses in fruit flies and examine whether animals mutant for DHR96, an ortholog of xenobiotic nuclear receptors PXR and CAR, plays a role in mediating xenobiotic responses in Drosophila.
The DHR96 nuclear receptor regulates xenobiotic responses in Drosophila.
No sample metadata fields
View SamplesTransgenerational effects of parental metabolic state have been shown, but the mechanism is still unclear. Here we present transcriptome sequencing data from AKHR heterozygous F1 progeny, either from obese maternal or paternal parents, compared to genetically matched heterozygous controls or to wild-type controls Overall design: 3 AKHR heterozygous samples descended from obese maternal parents, 3 AKHR heterozygous samples descended from obese paternal parents, 3 AKHR heterozygous samples descended from non-obese parents, and 3 wild-type controls, independent biological replicates and independent experimental replicates (1 set of samples from each experimental replicate)
Parental obesity leads to metabolic changes in the F2 generation in <i>Drosophila</i>.
Specimen part, Subject
View SamplesDHR96 plays a role in regulating xenobiotic responses in Drosophila. Using a gain-of-function approach we test whether DHR96 is sufficient to affect detoxification genes in the absence of a xenobiotic insult.
The DHR96 nuclear receptor regulates xenobiotic responses in Drosophila.
No sample metadata fields
View SamplesCancer cells utilize a unique form of aerobic glycolysis, called the Warburg effect, to efficiently produce the macromolecules required for proliferation. Here we show that a metabolic program related to the Warburg effect is used during normal Drosophila development and regulated by the fly ortholog of the Estrogen-Related Receptor (ERR) family of nuclear receptors. dERR null mutants die as second instar larvae with abnormally low ATP levels, diminished triacylglyceride stores, and elevated levels of circulating sugars. Metabolomic profiling revealed that the pathways affected in these mutants correspond to those used in the Warburg effect. The expression of active dERR protein in mid-embryogenesis triggers a coordinate switch in gene expression that drives a metabolic program supporting the dramatic growth that occurs during larval development. This study suggests that mammalian ERR family members may promote cancer by directing a metabolic state that supports proliferation.
The Drosophila estrogen-related receptor directs a metabolic switch that supports developmental growth.
Specimen part
View SamplesKnowing the gene expression profiles of drug-metabolizing enzymes and transporters throughout gestation is important for understanding the mechanisms of pregnancy-induced changes in drug pharmacokinetics. In this study, we compared gene expression of drug-metabolizing enzymes and transporters in the maternal liver, kidney, small intestine, and placenta of pregnant mice throughout gestation by microarray analysis. Specifically, we investigated cytochrome P450 (Cyp), UDP-glucuronosyltranserase (Ugt), and sulfotransferase (Sult), as well as ATP-binding cassette (Abc) and solute carrier (Slc) transporters. We found that relatively few Ugt and Sult genes were impacted by pregnancy in maternal tissues and placenta. Cyp1a2, most Cyp2 isoforms, Cyp3a11, and Cyp3a13 in the liver were down-regulated, with the greatest changes occurring on gestation days (gd) 15 and 19 compared to non-pregnant controls (gd 0). However, Cyp2d40, Cyp3a16, Cyp3a41a, Cyp3a41b, and Cyp3a44 in the liver were induced throughout pregnancy. Cyp expression in mid-gestation placenta (gd 10 and 15) was generally greater than that in term placenta (gd 19). There were also notable changes in Abc and Slc transporters. Abcc3 in the liver was down-regulated by 60%, and Abcb1a, Abcc4, and Slco4c1 in the kidney were down-regulated by 30-60% on gd 15 and 19 versus gd 0. Abcc5 in the placenta was induced 3-fold on gd 10 versus gd 15 and 19, whereas Slc22a3 expression in the placenta on gd 10 was 90% lower than that on gd 15 and 19. Overall, this study demonstrates important gestational age-dependent expression of drug-metabolizing enzymes and transporter genes, which may have mechanistic relevance to human pregnancy.
Gestational age-dependent changes in gene expression of metabolic enzymes and transporters in pregnant mice.
Specimen part
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