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Omega-3 Fatty Acids Modulate TRPV4 Function through Plasma Membrane Remodeling.

ABSTRACT: Dietary consumption of ω-3 polyunsaturated fatty acids (PUFAs), present in fish oils, is known to improve the vascular response, but their molecular targets remain largely unknown. Activation of the TRPV4 channel has been implicated in endothelium-dependent vasorelaxation. Here, we studied the contribution of ω-3 PUFAs to TRPV4 function by precisely manipulating the fatty acid content in Caenorhabditis elegans. By genetically depriving the worms of PUFAs, we determined that the metabolism of ω-3 fatty acids is required for TRPV4 activity. Functional, lipid metabolome, and biophysical analyses demonstrated that ω-3 PUFAs enhance TRPV4 function in human endothelial cells and support the hypothesis that lipid metabolism and membrane remodeling regulate cell reactivity. We propose a model whereby the eicosanoid's epoxide group location increases membrane fluidity and influences the endothelial cell response by increasing TRPV4 channel activity. ω-3 PUFA-like molecules might be viable antihypertensive agents for targeting TRPV4 to reduce systemic blood pressure.

SUBMITTER: Caires R

PROVIDER: S-EPMC8611619 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Omega-3 Fatty Acids Modulate TRPV4 Function through Plasma Membrane Remodeling.

Caires Rebeca R Sierra-Valdez Francisco J FJ Millet Jonathan R M JRM Herwig Joshua D JD Roan Esra E Vásquez Valeria V Cordero-Morales Julio F JF

Cell reports 20171001 1

Dietary consumption of ω-3 polyunsaturated fatty acids (PUFAs), present in fish oils, is known to improve the vascular response, but their molecular targets remain largely unknown. Activation of the TRPV4 channel has been implicated in endothelium-dependent vasorelaxation. Here, we studied the contribution of ω-3 PUFAs to TRPV4 function by precisely manipulating the fatty acid content in Caenorhabditis elegans. By genetically depriving the worms of PUFAs, we determined that the metabolism of ω-3 ...[more]

PMID: 28978477

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Project description:BackgroundOmega-3 polyunsaturated fatty acids (PUFAs) were proposed to have potential effects against inflammation and cancer. However, results from epidemiology studies remain inconsistent. We aimed to explore the associations of plasma PUFAs with EC recurrence and all-cause mortality.MethodWomen diagnosed with endometrial cancer (EC) between 2008 and 2013 and underwent surgery at Fudan University Shanghai Cancer Center of China were recruited. Survival status was followed up through September 2017. EC recurrence and total cause deaths were identified through medical record and telephone interview. In total, 202 patients with enough plasma samples at time of surgery were included. There were 195 patients who provided baseline plasma and survival information included in the current study. Plasma omega-3 PUFAs were measured by GC-FID. Cox Proportional Hazard model adjusted for potential cofounders was used to estimate HRs and 95% CIs.ResultsMedian follow-up time for patients was 58 months after surgery. A total of 13 recurrences and 11 all-cause deaths, of which, 2 deaths from EC, were identified. Level of plasma EPA was higher in recurrent patients than total patients (0.78% vs 0.51%, P = 0.015). Higher plasma eicosapentaenoic acid (EPA) level trended to have positive association with EC recurrence (P-trend = 0.04), although comparing to the lowest tertile, the highest tertile of EPA level was not significantly associated with increased risk of EC recurrence (HRT3vsT1 = 6.02; 95%CI = 0.7-52.06). The association between total omega-3 PUFA and EC recurrence tended to be stronger among patients with deeper myometrial invasion (OR = 3.41; 95%CI = 1.06-10.95; P-interaction = 0.04).ConclusionsHigher plasma EPA level was significantly associated with EC recurrence. Further studies are warranted to confirm these findings.Trial registrationChiCTR1900025418; Retrospectively registered (26 August 2019); Chinses Clinical Trial Registry.

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Omega-3 Fatty Acids Modulate TRPV4 Function through Plasma Membrane Remodeling.

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Omega-3 Fatty Acids Modulate TRPV4 Function through Plasma Membrane Remodeling.

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