ArticleStem cells and development2010
Epoxyeicosatrienoic acid agonist regulates human mesenchymal stem cell-derived adipocytes through activation of HO-1-pAKT signaling and a decrease in PPARγ.
Article in Stem cells and development, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
61 citing papers in PubMed, 102 citations in OpenAlex.
- GSK2256294 Decreases sEH (Soluble Epoxide Hydrolase) Activity in Plasma, Muscle, and Adipose and Reduces F2-Isoprostanes but Does Not Alter Insulin Sensitivity in Humans.Hypertension (Dallas, Tex. : 1979) · 2021Trial
- Impact of weight reduction on insulin resistance, adhesive molecules and adipokines dysregulation among obese type 2 diabetic patients.African health sciences · 2018Trial
- Impact of green tea on obesity-related hormones in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials.Avicenna journal of phytomedicine · 2026Review
- The Role of Adipokines in Health and Disease.Biomedicines · 2023Review
- 11,12-EET Regulates PPAR-γ Expression to Modulate TGF-β-Mediated Macrophage Polarization.Cells · 2023Article
- Article
- CYP450 Epoxygenase Metabolites, Epoxyeicosatrienoic Acids, as Novel Anti-Inflammatory Mediators.Molecules (Basel, Switzerland) · 2022Review
- Heme-oxygenase and lipid mediators in obesity and associated cardiometabolic diseases: Therapeutic implications.Pharmacology & therapeutics · 2022Review
- Serum Bilirubin Levels in Overweight and Obese Individuals: The Importance of Anti-Inflammatory and Antioxidant Responses.Antioxidants (Basel, Switzerland) · 2021Review
- Article
- Adiponectin: Structure, Physiological Functions, Role in Diseases, and Effects of Nutrition.Nutrients · 2021Review
- Brown Fat-Activating Lipokine 12,13-diHOME in Human Milk Is Associated With Infant Adiposity.The Journal of clinical endocrinology and metabolism · 2021Article
- Association of High Serum Adiponectin Level With Adverse Cardiovascular Outcomes and Progression of Coronary Artery Calcification in Patients With Pre-dialysis Chronic Kidney Disease.Frontiers in cardiovascular medicine · 2021Article
- Soluble Epoxide Hydrolase Inhibition byInternational journal of molecular sciences · 2020Article
- The Peroxisome Proliferator-Activated Receptor-Gamma Coactivator-1α-Heme Oxygenase 1 Axis, a Powerful Antioxidative Pathway with Potential to Attenuate Diabetic Cardiomyopathy.Antioxidants & redox signaling · 2020Review
- Heme Oxygenase-1 Upregulation: A Novel Approach in the Treatment of Cardiovascular Disease.Antioxidants & redox signaling · 2020Review
- SERUM BILIRUBIN CORRELATES WITH SERUM ADIPOKINES IN NORMAL WEIGHT AND OVERWEIGHT ASYMPTOMATIC ADULTS.Acta clinica Croatica · 2020Article
- Small molecules for mesenchymal stem cell fate determination.World journal of stem cells · 2019Review
- Mechanistic Insight of Na/K-ATPase Signaling and HO-1 into Models of Obesity and Nonalcoholic Steatohepatitis.International journal of molecular sciences · 2019Review
- HO-1 overexpression and underexpression: Clinical implications.Archives of biochemistry and biophysics · 2019Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Human mesenchymal stem cells (MSCs) expressed substantial levels of CYP2J2, a major CYP450 involved in epoxyeicosatrienoic acid (EET) formation. MSCs synthesized significant levels of EETs (65.8 ± 5.8 pg/mg protein) and dihydroxyeicosatrienoic acids (DHETs) (15.83 ± 1.62 pg/mg protein), suggesting the presence of soluble epoxide hydrolase (sEH). The addition of an sEH inhibitor to MSC culture decreased adipogenesis. EETs decreased MSC-derived adipocytes in a concentration-dependent manner, 8,9- and 14,15-EET having the maximum reductive effect on adipogenesis. We examined the effect of 12-(3-hexylureido)dodec-8(Z)-enoic acid, an EET agonist, on MSC-derived adipocytes and demonstrated an increased number of healthy small adipocytes, attenuated fatty acid synthase (FAS) levels (P < 0.01), and reduced PPARγ, C/EBPα, FAS, and lipid accumulation (P < 0.05). These effects were accompanied by increased levels of heme oxygenase (HO)-1 and adiponectin (P < 0.05), and increased glucose uptake (P < 0.05). Inhibition of HO activity or AKT by tin mesoporphyrin (SnMP) and LY2940002, respectively, reversed EET-induced inhibition of adipogenesis, suggesting that activation of the HO-1-adiponectin axis underlies EET effect in MSCs. These findings indicate that EETs decrease MSC-derived adipocyte stem cell differentiation by upregulation of HO-1-adiponectin-AKT signaling and play essential roles in the regulation of adipocyte differentiation by inhibiting PPARγ, C/EBPα, and FAS and in stem cell development. These novel observations highlight the seminal role of arachidonic acid metabolism in MSCs and suggest that an EET agonist may have potential therapeutic use in the treatment of dyslipidemia, diabetes, and the metabolic syndrome.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.