ArticleJournal of advanced research2023
CRISPR/Cas9-mediated inactivation of the phosphatase activity of soluble epoxide hydrolase prevents obesity and cardiac ischemic injury.
Article in Journal of advanced research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- Fragment-Based Discovery of Fenamic Acids as Pan-Species Inhibitors of the Soluble Epoxide Hydrolase Phosphatase Domain.ACS chemical biology · 2026Article
- Inactivation of the Phosphatase Activity of Soluble Epoxide Hydrolase Modulates SIRT3 and Attenuates Experimental Pulmonary Hypertension.Comprehensive Physiology · 2026Article
- The phosphatase activity of soluble epoxide hydrolase regulates vascular calcification through the metabolism of pyrophosphate anions.Cell death & disease · 2025Article
- Structure-Based Design of PROTACS for the Degradation of Soluble Epoxide Hydrolase.Journal of medicinal chemistry · 2025Article
- Cold exposure and the cardiovascular system: from physiological adaptation to pathological risk.Frontiers in physiology · 2025Review
- Mice deficient in the phosphatase activity of sEH show decreased levels of the endocannabinoid 2-AG in the olfactory bulb and depressive-like behavior.FEBS letters · 2024Article
- From Classical to Alternative Pathways of 2-Arachidonoylglycerol Synthesis: AlterAGs at the Crossroad of Endocannabinoid and Lysophospholipid Signaling.Molecules (Basel, Switzerland) · 2024Review
- CRISPR/Cas9 Technology: A Novel Approach to Obesity Research.Current pharmaceutical design · 2024Review
- The involvement of soluble epoxide hydrolase in the development of cardiovascular diseases through epoxyeicosatrienoic acids.Frontiers in pharmacology · 2024Review
- Soluble epoxide hydrolase maintains steady-state lipid turnover linked with autocrine signaling in peritoneal macrophages.iScience · 2023Article
- Small Molecule Activation of NAPE-PLD Enhances Efferocytosis by Macrophages.ACS chemical biology · 2023Article
- Small Molecule Activation of NAPE-PLD Enhances Efferocytosis by Macrophages.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
44 authors at 8 institutions in 2 countries.
Funding
Abstract
introductionAlthough the physiological role of the C-terminal hydrolase domain of the soluble epoxide hydrolase (sEH-H) is well investigated, the function of its N-terminal phosphatase activity (sEH-P) remains unknown.
objectivesThis study aimed to assess in vivo the physiological role of sEH-P.
methodsCRISPR/Cas9 was used to generate a novel knock-in (KI) rat line lacking the sEH-P activity.
resultsThe sEH-P KI rats has a decreased metabolism of lysophosphatidic acids to monoacyglycerols. KI rats grew almost normally but with less weight and fat mass gain while insulin sensitivity was increased compared to wild-type rats. This lean phenotype was more marked in males than in female KI rats and mainly due to decreased food consumption and enhanced energy expenditure. In fact, sEH-P KI rats had an increased lipolysis allowing to supply fatty acids as fuel to potentiate brown adipose thermogenesis under resting condition and upon cold exposure. The potentiation of thermogenesis was abolished when blocking PPARγ, a nuclear receptor activated by intracellular lysophosphatidic acids, but also when inhibiting simultaneously sEH-H, showing a functional interaction between the two domains. Furthermore, sEH-P KI rats fed a high-fat diet did not gain as much weight as the wild-type rats, did not have increased fat mass and did not develop insulin resistance or hepatic steatosis. In addition, sEH-P KI rats exhibited enhanced basal cardiac mitochondrial activity associated with an enhanced left ventricular contractility and were protected against cardiac ischemia-reperfusion injury.
conclusionOur study reveals that sEH-P is a key player in energy and fat metabolism and contributes together with sEH-H to the regulation of cardiometabolic homeostasis. The development of pharmacological inhibitors of sEH-P appears of crucial importance to evaluate the interest of this promising therapeutic strategy in the management of obesity and cardiac ischemic complications.
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