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Drosophila Gr64e mediates fatty acid sensing via the phospholipase C pathway.

ABSTRACT: Animals use taste to sample and ingest essential nutrients for survival. Free fatty acids (FAs) are energy-rich nutrients that contribute to various cellular functions. Recent evidence suggests FAs are detected through the gustatory system to promote feeding. In Drosophila, phospholipase C (PLC) signaling in sweet-sensing cells is required for FA detection but other signaling molecules are unknown. Here, we show Gr64e is required for the behavioral and electrophysiological responses to FAs. GR64e and TRPA1 are interchangeable when they act downstream of PLC: TRPA1 can substitute for GR64e in FA but not glycerol sensing, and GR64e can substitute for TRPA1 in aristolochic acid but not N-methylmaleimide sensing. In contrast to its role in FA sensing, GR64e functions as a ligand-gated ion channel for glycerol detection. Our results identify a novel FA transduction molecule and reveal that Drosophila Grs can act via distinct molecular mechanisms depending on context.

SUBMITTER: Kim H

PROVIDER: S-EPMC5821400 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Drosophila Gr64e mediates fatty acid sensing via the phospholipase C pathway.

Kim Hyeyon H Kim Haein H Kwon Jae Young JY Seo Jeong Taeg JT Shin Dong Min DM Moon Seok Jun SJ

PLoS genetics 20180208 2

Animals use taste to sample and ingest essential nutrients for survival. Free fatty acids (FAs) are energy-rich nutrients that contribute to various cellular functions. Recent evidence suggests FAs are detected through the gustatory system to promote feeding. In Drosophila, phospholipase C (PLC) signaling in sweet-sensing cells is required for FA detection but other signaling molecules are unknown. Here, we show Gr64e is required for the behavioral and electrophysiological responses to FAs. GR64 ...[more]

PMID: 29420533

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Project description:Oleanolic acid (OA) is reported to possess antihypertensive activity via the regulation of lipid metabolism; however, the mechanisms underlying lipid regulation by OA are yet to be fully elucidated. The aim of the present study was to evaluate the mechanisms via which OA regulates lipid metabolism in spontaneously hypertensive rats (SHRs) via ultra‑performance liquid chromatography‑quadrupole/Orbitrap‑mass spectrometry (MS)‑based lipidomics analysis. SHRs were treated with OA (1.08 mg/kg) for 4 weeks. The liver tissues were excised, homogenized in dichloromethane and centrifuged, and subsequently the supernatant layer was collected and concentrated under vacuum to dryness. The dichloromethane extract was subjected to MS analysis and database searching, and comparison of standards was performed to identify potential biomarkers. Partial least squares‑discriminant analysis performed on the liver lipidome revealed a total of 14 endogenous metabolites that were significantly changed in the SHR model group (SH group) compared with Wistar Kyoto rats [normal control (NC group)], including glycerophospholipids, sphingolipids and glycerides. Heatmaps revealed that the liver lipid profiles in the OA group were clustered more closely compared with those observed in the NC group, indicating that the antihypertensive effect of OA was mediated via regulation of liver lipid metabolites. It was observed that the protein levels of secretory phospholipase A2 (sPLA2) and fatty acid synthase (FAS) were increased in the SH group compared with the NC group. In addition, the levels of lysophosphatidylcholine and triglycerides in the liver were elevated, whereas the levels of low‑density lipoprotein cholesterol and high‑density lipoprotein cholesterol were reduced in the SH group. Upon treatment with OA, the mRNA and protein levels of PLA2 and FAS were observed to be downregulated. Collectively, the present study indicated that the antihypertensive activity of OA was mediated via downregulation of sPLA2 and FAS in SHRs, and that treatment with OA resulted in significant improvements in blood pressure and associated abnormalities in the lipid metabolites.

Dataset Information

Drosophila Gr64e mediates fatty acid sensing via the phospholipase C pathway.

Publications

Drosophila Gr64e mediates fatty acid sensing via the phospholipase C pathway.

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