Evidence map›Paper›PMID 23103940›Full record

ArticleNature chemical biology2012

DAGLβ inhibition perturbs a lipid network involved in macrophage inflammatory responses.

Ku-Lung Hsu, Katsunori Tsuboi, Alexander Adibekian, Holly Pugh, Kim Masuda, Benjamin F Cravatt

Open access · greenAbstract read
In one paragraph

Article in Nature chemical biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
133citing papers in PubMed, 1 pooled it
13.8field-weighted citation impact, top 1% 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

133 citing papers in PubMed, 1 synthesis or guideline pooled it, 218 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Chemical Probes for Investigating the Endocannabinoid System.Current topics in behavioral neurosciences · 2026
    Review
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  7. Article
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  9. Article
  10. Article
  11. Review
  12. P2XBritish journal of pharmacology · 2024
    Article
  13. Beyond dopamine: exploring endocannabinoids in Parkinson's disease.Ageing and neurodegenerative diseases · 2024
    Article
  14. Endocannabinoid biosynthetic enzymes regulate pain response via LKB1-AMPK signaling.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Article

73 more citing papers are in PubMed but not listed here.

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

6 authors at 1 institution in 1 country.

Ku-Lung HsuThe Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA.
Katsunori Tsuboi
Alexander Adibekian
Holly Pugh
Kim Masuda
Benjamin F Cravatt
Scripps Research Institute · US

Funding

UHTS Implementation(Florida)U54MH084512 · NIMH · SCRIPPS RESEARCH INSTITUTE, THE · PI DING, SHENG · 2008 to 2013
$89.2M
SYNTHESIS OF SR141716A AND ANANDAMIDE ANALOGSP01DA009789 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI CRAVATT, BENJAMIN F · 1995 to 2013
$11.6M
CHEMOPROTEOMIC METHODS FOR SERINE HYDROLASE INHIBITOR DEVELOPMENTR01DA033760 · NIDA · SCRIPPS RESEARCH INSTITUTE, THE · PI CRAVATT, BENJAMIN F, SCAMPAVIA, LOUIS DANIEL · 2012 to 2021
$5.1M
NIDA NIH HHS DA009789NIDA NIH HHS DA033760NIDA NIH HHS P01 DA009789NIDA NIH HHS R01 DA033760NIMH NIH HHS MH084512NIMH NIH HHS U54 MH084512
6 · The paper itself

Abstract

The endocannabinoid 2-arachidonoylglycerol (2-AG) is biosynthesized by diacylglycerol lipases DAGLα and DAGLβ. Chemical probes to perturb DAGLs are needed to characterize endocannabinoid function in biological processes. Here we report a series of 1,2,3-triazole urea inhibitors, along with paired negative-control and activity-based probes, for the functional analysis of DAGLβ in living systems. Optimized inhibitors showed high selectivity for DAGLβ over other serine hydrolases, including DAGLα (∼60-fold selectivity), and the limited off-targets, such as ABHD6, were also inhibited by the negative-control probe. Using these agents and Daglb(-/-) mice, we show that DAGLβ inactivation lowers 2-AG, as well as arachidonic acid and eicosanoids, in mouse peritoneal macrophages in a manner that is distinct and complementary to disruption of cytosolic phospholipase-A2. We observed a corresponding reduction in lipopolysaccharide-induced tumor necrosis factor-α release. These findings indicate that DAGLβ is a key metabolic hub within a lipid network that regulates proinflammatory responses in macrophages.

Indexed as

AnimalsArachidonic AcidArachidonic AcidsCell LineCytokinesDrug DiscoveryEndocannabinoidsGlyceridesInflammationLipid MetabolismLipoprotein LipaseMacrophages, PeritonealMiceMice, KnockoutNeuronsProstaglandinsArachidonic AcidArachidonic AcidsCytokinesdiacylglycerol lipase beta, mouseEndocannabinoidsGlyceridesglyceryl 2-arachidonateLipoprotein LipaseProstaglandinsProtein IsoformsProteomeTriazolesTumor Necrosis Factor-alpha

Identifiers

PMID23103940
PMCPMC3513945
OpenAlexW2134450626

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.