Abstract
Transient receptor potential (TRP) cation channels are highly conserved in humans and insects. Some of these channels are expressed in internal organs and their functions remain incompletely understood. By direct knock-in of the GAL4 gene into the trpA1 locus in Drosophila, we identified the expression of this gene in the subesophageal ganglion (SOGs) region. In addition, the neurites present in the dorsal posterior region as well as the drosophila insulin-like peptide 2 (dILP2)-positive neurons send signals to the SOGs. The signal is sent to the crop, which is an enlarged organ of the esophagus and functions as a storage place for food in the digestive system. To systematically investigate the role of TRPA1 in metabolism, we applied non-targeted metabolite profiling analysis together with gas-chromatography/time-of-flight mass spectrometry, with an aim to identify a wide range of primary metabolites. We effectively captured distinctive metabolomic phenotypes and identified specific metabolic dysregulation triggered by TRPA1 mutation based on reconstructed metabolic network analysis. Primarily, the network analysis pinpointed the simultaneous down-regulation of intermediates in the methionine salvation pathway, in contrast to the synchronized up-regulation of a range of free fatty acids. The gene dosage-dependent dynamics of metabolite levels among wild-type, hetero- and homozygous mutants, and their coordinated metabolic modulation under multiple gene settings across five different genotypes confirmed the direct linkages of TRPA1 to metabolism.
Highlights
The gastrointestinal tract is a digestive organ system responsible for controlling ingestion, digestion, absorption, and excretion
Integrative statistical analysis revealed the direct effect of TRPA1 mutation on methionine salvage pathway and free fatty acid metabolism and confirmed it by exploring the metabolic dynamics under multiple gene settings, including trpA11, UAS-trpA1;trpA1GAL4, and trpA1GAL4, which imply the direct effect of TRPA1 on the metabolism
We recently showed that TRPA1 has a role associated with circadian pacemaker neurons in adult brain [6]
Summary
The gastrointestinal tract is a digestive organ system responsible for controlling ingestion, digestion, absorption, and excretion. Integrative statistical analysis revealed the direct effect of TRPA1 mutation on methionine salvage pathway and free fatty acid metabolism and confirmed it by exploring the metabolic dynamics under multiple gene settings, including trpA11, UAS-trpA1;trpA1GAL4, and trpA1GAL4, which imply the direct effect of TRPA1 on the metabolism. The clustering analysis allowed a more detailed insight; certain groups of chemicals showed biochemical relevance with a co-regulatory expression pattern in accordance with the different genotypes (Fig 2B).
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