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Drosophila Estrogen-Related Receptor directs a transcriptional switch that supports adult glycolysis and lipogenesis

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE144766 | GEO | 2020/03/01

REPOSITORIES: GEO

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<i>Drosophila</i> estrogen-related receptor directs a transcriptional switch that supports adult glycolysis and lipogenesis.

Project description:Metabolism and development must be closely coupled to meet the changing physiological needs of each stage in the life cycle. The molecular mechanisms that link these pathways, however, remain poorly understood. Here we show that the Drosophila estrogen-related receptor (dERR) directs a transcriptional switch in mid-pupae that promotes glucose oxidation and lipogenesis in young adults. dERR mutant adults are viable but display reduced locomotor activity, susceptibility to starvation, elevated glucose, and an almost complete lack of stored triglycerides. Molecular profiling by RNA-seq, ChIP-seq, and metabolomics revealed that glycolytic and pentose phosphate pathway genes are induced by dERR, and their reduced expression in mutants is accompanied by elevated glycolytic intermediates, reduced TCA cycle intermediates, and reduced levels of long chain fatty acids. Unexpectedly, we found that the central pathways of energy metabolism, including glycolysis, the tricarboxylic acid cycle, and electron transport chain, are coordinately induced at the transcriptional level in mid-pupae and maintained into adulthood, and this response is partially dependent on dERR, leading to the metabolic defects observed in mutants. Our data support the model that dERR contributes to a transcriptional switch during pupal development that establishes the metabolic state of the adult fly.

| S-EPMC7197351 | biostudies-literature

Drosophila Estrogen-Related Receptor directs a transcriptional switch that supports adult glycolysis and lipogenesis [ChIP-Seq]

Project description:Metabolism and development must be closely coupled to meet the changing physiological needs of each stage in the life cycle. The molecular mechanisms that link these pathways, however, remain poorly understood. Here we show that the Drosophila Estrogen-Related Receptor (dERR) directs a transcriptional switch in mid-pupae that promotes glucose oxidation and lipogenesis in young adults. dERR mutant adults are viable but display reduced locomotor activity, susceptibility to starvation, elevated glucose and an almost complete lack of stored triglycerides. Molecular profiling by RNA-seq, ChIP-seq, and metabolomics revealed that glycolytic and pentose phosphate pathway genes are induced by dERR, and their reduced expression in mutants is accompanied by elevated glycolytic intermediates, reduced TCA cycle intermediates, and reduced levels of long chain fatty acids. Unexpectedly, we find that the central pathways of energy metabolism, including glycolysis, the tricarboxylic acid cycle, and electron transport chain, are coordinately induced at the transcriptional level in mid-pupae and maintained into adulthood, and this response is partially dependent on dERR, leading to the metabolic defects observed in mutants. Our data support the model that dERR contributes to a transcriptional switch during pupal development that establishes the metabolic state of the adult fly.

2020-03-01 | GSE144763 | GEO

Drosophila Estrogen-Related Receptor directs a transcriptional switch that supports adult glycolysis and lipogenesis [RNA-Seq timecourse]

Project description:Metabolism and development must be closely coupled to meet the changing physiological needs of each stage in the life cycle. The molecular mechanisms that link these pathways, however, remain poorly understood. Here we show that the Drosophila Estrogen-Related Receptor (dERR) directs a transcriptional switch in mid-pupae that promotes glucose oxidation and lipogenesis in young adults. dERR mutant adults are viable but display reduced locomotor activity, susceptibility to starvation, elevated glucose and an almost complete lack of stored triglycerides. Molecular profiling by RNA-seq, ChIP-seq, and metabolomics revealed that glycolytic and pentose phosphate pathway genes are induced by dERR, and their reduced expression in mutants is accompanied by elevated glycolytic intermediates, reduced TCA cycle intermediates, and reduced levels of long chain fatty acids. Unexpectedly, we find that the central pathways of energy metabolism, including glycolysis, the tricarboxylic acid cycle, and electron transport chain, are coordinately induced at the transcriptional level in mid-pupae and maintained into adulthood, and this response is partially dependent on dERR, leading to the metabolic defects observed in mutants. Our data support the model that dERR contributes to a transcriptional switch during pupal development that establishes the metabolic state of the adult fly.

2020-03-01 | GSE144764 | GEO

Drosophila Estrogen-Related Receptor directs a transcriptional switch that supports adult glycolysis and lipogenesis [RNA-Seq d6]

Project description:Metabolism and development must be closely coupled to meet the changing physiological needs of each stage in the life cycle. The molecular mechanisms that link these pathways, however, remain poorly understood. Here we show that the Drosophila Estrogen-Related Receptor (dERR) directs a transcriptional switch in mid-pupae that promotes glucose oxidation and lipogenesis in young adults. dERR mutant adults are viable but display reduced locomotor activity, susceptibility to starvation, elevated glucose and an almost complete lack of stored triglycerides. Molecular profiling by RNA-seq, ChIP-seq, and metabolomics revealed that glycolytic and pentose phosphate pathway genes are induced by dERR, and their reduced expression in mutants is accompanied by elevated glycolytic intermediates, reduced TCA cycle intermediates, and reduced levels of long chain fatty acids. Unexpectedly, we find that the central pathways of energy metabolism, including glycolysis, the tricarboxylic acid cycle, and electron transport chain, are coordinately induced at the transcriptional level in mid-pupae and maintained into adulthood, and this response is partially dependent on dERR, leading to the metabolic defects observed in mutants. Our data support the model that dERR contributes to a transcriptional switch during pupal development that establishes the metabolic state of the adult fly.

2020-03-01 | GSE144762 | GEO

Drosophila Estrogen-Related Receptor directs a transcriptional switch that supports adult glycolysis and lipogenesis

Project description:Drosophila Estrogen-Related Receptor directs a transcriptional switch that supports adult glycolysis and lipogenesis

| PRJNA604799 | ENA

The Drosophila estrogen-related receptor directs a metabolic switch that supports developmental growth.

Project description:Metabolism must be coordinated with development to provide the appropriate energetic needs for each stage in the life cycle. Little is known, however, about how this temporal control is achieved. Here, we show that the Drosophila ortholog of the estrogen-related receptor (ERR) family of nuclear receptors directs a critical metabolic transition during development. dERR mutants die as larvae with low ATP levels and elevated levels of circulating sugars. The expression of active dERR protein in mid-embryogenesis triggers a coordinate switch in gene expression that drives a metabolic program normally associated with proliferating cells, supporting the dramatic growth that occurs during larval development. This study shows that dERR plays a central role in carbohydrate metabolism, demonstrates that a proliferative metabolic program is used in normal developmental growth, and provides a molecular context to understand the close association between mammalian ERR family members and cancer.

| S-EPMC3072597 | biostudies-literature

Drosophila Estrogen-Related Receptor directs a transcriptional switch that supports adult glycolysis and lipogenesis [ChIP-Seq]

Project description:Drosophila Estrogen-Related Receptor directs a transcriptional switch that supports adult glycolysis and lipogenesis [ChIP-Seq]

| PRJNA604806 | ENA

Drosophila Estrogen-Related Receptor directs a transcriptional switch that supports adult glycolysis and lipogenesis [RNA-Seq timecourse]

Project description:Drosophila Estrogen-Related Receptor directs a transcriptional switch that supports adult glycolysis and lipogenesis [RNA-Seq timecourse]

| PRJNA604805 | ENA

Drosophila Estrogen-Related Receptor directs a transcriptional switch that supports adult glycolysis and lipogenesis [RNA-Seq d6]

Project description:Drosophila Estrogen-Related Receptor directs a transcriptional switch that supports adult glycolysis and lipogenesis [RNA-Seq d6]

| PRJNA604807 | ENA

Drosophila HNF4 Directs a Switch in Lipid Metabolism that Supports the Transition to Adulthood.

Project description:Animals must adjust their metabolism as they progress through development in order to meet the needs of each stage in the life cycle. Here, we show that the dHNF4 nuclear receptor acts at the onset of Drosophila adulthood to direct an essential switch in lipid metabolism. Lipid stores are consumed shortly after metamorphosis but contribute little to energy metabolism. Rather, dHNF4 directs their conversion to very long chain fatty acids and hydrocarbons, which waterproof the animal to preserve fluid homeostasis. Similarly, HNF4? is required in mouse hepatocytes for the expression of fatty acid elongases that contribute to a waterproof epidermis, suggesting that this pathway is conserved through evolution. This developmental switch in Drosophila lipid metabolism promotes lifespan and desiccation resistance in adults and suppresses hallmarks of diabetes, including elevated glucose levels and intolerance to dietary sugars. These studies establish dHNF4 as a regulator of the adult metabolic state.

| S-EPMC6351194 | biostudies-literature