Small molecule drug screening in Drosophila identifies the 5HT2A receptor as a feeding modulation target
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This work used Drosophila melanogaster larvae to develop a high-throughput whole organism screen for drugs that modulate food intake and identified the serotonin (5-hydroxytryptamine or 5-HT) receptor antagonist metitepine as a potent anorectic drug.Abstract:
Dysregulation of eating behavior can lead to obesity, which affects 10% of the adult population worldwide and accounts for nearly 3 million deaths every year. Despite this burden on society, we currently lack effective pharmacological treatment options to regulate appetite. We used Drosophila melanogaster larvae to develop a high-throughput whole organism screen for drugs that modulate food intake. In a screen of 3630 small molecules, we identified the serotonin (5-hydroxytryptamine or 5-HT) receptor antagonist metitepine as a potent anorectic drug. Using cell-based assays we show that metitepine is an antagonist of all five Drosophila 5-HT receptors. We screened fly mutants for each of these receptors and found that serotonin receptor 5-HT2A is the sole molecular target for feeding inhibition by metitepine. These results highlight the conservation of molecular mechanisms controlling appetite and provide a method for unbiased whole-organism drug screens to identify novel drugs and molecular pathways modulating food intake.read more
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National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9·1 million participants
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TL;DR: It is suggested that brain IPCs are the main systemic supply of insulin during larval growth and pancreatic islet β cells are functionally analogous and may have evolved from a common ancestral insulin-producing neuron.
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A conditional tissue-specific transgene expression system using inducible GAL4
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