Evidence map›Paper›PMID 30041041›Full record

ArticleProstaglandins & other lipid mediators2018

Ablation of soluble epoxide hydrolase reprogram white fat to beige-like fat through an increase in mitochondrial integrity, HO-1-adiponectin in vitro and in vivo.

Lu Liu, Nitin Puri, Marco Raffaele, Joseph Schragenheim, Shailendra P Singh, J Alyce Bradbury, Lars Bellner, Luca Vanella, Darryl C Zeldin, Jian Cao and 1 more

Abstract read
In one paragraph

Article in Prostaglandins & other lipid mediators, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.2field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 39 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
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  6. Article
  7. Article
  8. eLife · 2021
    Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Soluble Epoxide Hydrolase Inhibition byInternational journal of molecular sciences · 2020
    Article
  14. Review
  15. Review
  16. RETRACTED: Cold-PressedAntioxidants (Basel, Switzerland) · 2020
    Article
  17. Review
  18. Article
  19. Article
  20. HO-1 overexpression and underexpression: Clinical implications.Archives of biochemistry and biophysics · 2019
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 3 countries.

Lu LiuDepartment of Cardiology, Nanlou Division, Chinese PLA General Hospital, National Clinical Research Center for Geriatric Diseases, Beijing, 100853, China; Department of Pharmacology, New York Medical College, Valhalla, NY, 10595, USA.
Nitin PuriJoan Edward School of Medicine, Marshall University, Huntington, WV, 25701, USA.
Marco RaffaeleDepartment of Drug Sciences, University of Catania, Catania, Italy.
Joseph SchragenheimDepartment of Pharmacology, New York Medical College, Valhalla, NY, 10595, USA.
Shailendra P SinghDepartment of Pharmacology, New York Medical College, Valhalla, NY, 10595, USA.
J Alyce BradburyDivision of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA.
Lars BellnerDepartment of Pharmacology, New York Medical College, Valhalla, NY, 10595, USA.
Luca VanellaDepartment of Pharmacology, New York Medical College, Valhalla, NY, 10595, USA; Department of Drug Sciences, University of Catania, Catania, Italy.
Darryl C ZeldinDivision of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA.
Jian CaoDepartment of Cardiology, Nanlou Division, Chinese PLA General Hospital, National Clinical Research Center for Geriatric Diseases, Beijing, 100853, China. Electronic address: calvin301@163.com.
Nader G AbrahamDepartment of Pharmacology, New York Medical College, Valhalla, NY, 10595, USA; Joan Edward School of Medicine, Marshall University, Huntington, WV, 25701, USA. Electronic address: nader_abraham@nymc.edu.
New York Medical College · USNational Institute of Environmental Health Sciences · USChinese PLA General Hospital · CNMarshall University · USUniversity of Catania · IT

Funding

Characterization And Functional Significance Of P450 Arachidonate EpoxygenasesZIAES025034 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI ZELDIN, DARRYL C · 2009 to 2025
$18.6M
P450 Arachidonate EpoxygenasesZ01ES025034 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI ZELDIN, DARRYL C · 1995 to 2008
$2.2M
Intramural NIH HHS Z01 ES025034
6 · The paper itself

Abstract

We have shown that epoxyeicosatrienoic acids (EETs), specifically 11,12- and 14,15-EETs, reduce adipogenesis in human mesenchymal stem cells and mouse preadipocytes (3T-3L1). In this study, we explore the effects of soluble epoxide hydrolase (sEH) deletion on various aspects of adipocyte-function, including programing for white vs. beige-like fat, and mitochondrial and thermogenic gene-expressions. We further hypothesize that EETs and heme-oxygenase 1 (HO-1) form a synergistic, functional module whose effects on adipocyte and vascular function is greater than the effects of sEH deletion alone. In in vitro studies, we examined the effect of sEH inhibitors on MSC-derived adipocytes. MSC-derived adipocytes exposed to AUDA, an inhibitor of sEH, exhibit an increased number of small and healthy adipocytes, an effect reproduced by siRNA for sEH. in vivo studies indicate that sEH deletion results in a significant decrease in adipocyte size, inflammatory adipokines NOV, TNFα, while increasing adiponectin (p < 0.05). These findings are associated with a decrease in body weight (p < 0.05), and visceral fat (p < 0.05). Importantly, sEH deletion was associated with a significant increase in Mfn1, COX 1, UCP1 and adiponectin (p < 0.03). sEH deletion was manifested by a significant increase in EETs isomers 5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET and an increased EETs/DHETEs ratio. Notably, activation of HO-1 gene expression further increased the levels of EETs, suggesting that the antioxidant HO-1 system protects EETs from degradation by ROS. These results are novel in that sEH deletion, while increasing EET levels, resulted in reprograming of white fat to express mitochondrial and thermogenic genes, a phenotype characteristic of beige-fat. Thus, EETs agonist(s) and sEH inhibitors may have therapeutic potential in the treatment of metabolic syndrome and obesity.

Indexed as

3T3-L1 Cells8,11,14-Eicosatrienoic AcidAdipocytesAdiponectinAdipose Tissue, BeigeAdipose Tissue, WhiteAnimalsCells, CulturedEpoxide HydrolasesGene ExpressionHeme Oxygenase-1HumansMesenchymal Stem CellsMiceMice, KnockoutMitochondria11,12-epoxy-5,8,14-eicosatrienoic acid14,15-epoxy-5,8,11-eicosatrienoic acid8,11,14-Eicosatrienoic AcidAdiponectinEpoxide HydrolasesHeme Oxygenase-1Vasodilator AgentsHeme OxygenaseMitochondrial proteinOxidative phosphorylationPGC-1 coactivatorsUncoupling protein 1 (UCP1)

Identifiers

PMID30041041
PMCPMC6314013
OpenAlexW2883878261

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.