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DAGLβ inhibition perturbs a lipid network involved in macrophage inflammatory responses
Open accessAbstract
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.
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“Importantly, DAGL-β inhibition also blocks the LPS-induced production of proinflammatory mediators (Hsu et al, 2012).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Hsu et al, 2012
In the citing paper
“Specifically, DAGL-β is highly expressed in macrophages, and its blockade leads to reduced levels of 2-AG, arachidonic acid, and a variety of proinflammatory arachidonic acid metabolites and proinflammatory cytokines in these cells (Hsu et al, 2012).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Hsu et al, 2012
In the citing paper
“The observation that selective inhibition of DAGL-β, the biosynthetic enzyme expressed predominantly on macrophages and microglia, reduces pro-inflammatory mediators (Hsu et al, 2012), and reverses nociceptive behavior in a mouse model of CCI (Wilkerson et al, 2016a) appears to be at odds with the antinociceptive effects of MAGL inhibitors in this same model.”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Hsu et al, 2012
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Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid Receptor
Devane, W. A., Hanuš, L., Breuer, A., Pertwee, R. G., Stevenson, L. A., Griffin, G., Gibson, D., Mandelbaum, A., Etinger, A., & Mechoulam, R. (1992) · Science · doi:10.1126/science.1470919 · Cited by 5,633
Ledent, C. A., Valverde, O., Cossu, G., Petitet, F., Aubert, J.-F., Beslot, F., Böhme, G. A., Impérato, A., Pedrazzini, T., Roques, B. P., et al. (1999) · Science · doi:10.1126/science.283.5400.401 · Cited by 3,628
Mechoulam, R., Ben-Shabat, S., Hanus, L., Ligumsky, M., Kaminski, N. E., Schatz, A. R., Gopher, A., Almog, S., Martin, B. R., Compton, D. R., et al. (1995) · Biochemical Pharmacology · doi:10.1016/0006-2952(95)00109-d · Cited by 2,913
2-Arachidonoylgylcerol: A Possible Endogenous Cannabinoid Receptor Ligand in Brain
Sugiura, T., Kondo, S., Sukagawa, A., Nakane, S., Shinoda, A., Itoh, K., Yamashita, A., & Waku, K. (1995) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1995.2437 · Cited by 2,196
Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides
Cravatt, B. F., Giang, D. K., Mayfield, S. P., Boger, D. L., Lerner, R. A., & Gilula, N. B. (1996) · Nature · doi:10.1038/384083a0 · Cited by 2,125
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Parameswaran, N., & Patial, S. (2010) · Critical Reviews in Eukaryotic Gene Expression · doi:10.1615/critreveukargeneexpr.v20.i2.10 · Cited by 1,490
Brain monoglyceride lipase participating in endocannabinoid inactivation
Dinh, T. P., Carpenter, D., Leslie, F. M., Freund, T. F., Katona, I., Sensi, S. L., Kathuria, S., & Piomelli, D. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.152334899 · Cited by 1,373
Modulation of anxiety through blockade of anandamide hydrolysis
Kathuria, S., Gaetani, S., Fegley, D., Valiño, F., Duranti, A., Tontini, A., Mor, M., Tarzia, G., Rana, G. L., Calignano, A., et al. (2003) · Nature Medicine · doi:10.1038/nm803 · Cited by 1,293
Activity-Based Protein Profiling: From Enzyme Chemistry to Proteomic Chemistry
Cravatt, B. F., Wright, A. T., & Kozarich, J. W. (2008) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.75.101304.124125 · Cited by 1,270
Self-citationA Comprehensive Profile of Brain Enzymes that Hydrolyze the Endocannabinoid 2-Arachidonoylglycerol
Blankman, J. L., Simon, G. M., & Cravatt, B. F. (2007) · Chemistry & Biology · doi:10.1016/j.chembiol.2007.11.006 · Cited by 1,177
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Items 201–236 of 236
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Chakraborty, A., Punnamraju, P., Sajeevan, T., Kaur, A., Kolthur‐Seetharam, U., & Kamat, S. S. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.06.02.597019 · Cited by 1
DAGLα/β, 2-AG release, and Parkinson’s Disease: Exploring a causal linkPreprint
Doherty, P., & Williams, G. (2025) · bioRxiv · doi:10.1101/2025.04.17.649373 · Cited by 1
Grams, R. J., Murtagh1, O. L., Ware, M. L., Vasylevskyi, S., & Hsu, K. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.27.702106 · Cited by 1
Self-citationThe endocannabinoid system : a translational study from Achilles tendinosis to cyclooxygenase
Björklund, E. (2014) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
Aaltonen, N. (2013) · UEF eRepo (University of Eastern Finland)
Discriminative Stimulus Properties of Endogenous Cannabinoid Degradative Enzyme Inhibitors
Owens, R. (2016) · VCU Scholars Compass (Virginia Commonwealth University) · doi:10.25772/h27y-zf33
Medina-Cleghorn, D. A. (2015) · eScholarship (California Digital Library)
Utilizing Chemoproteomic Platforms to Elucidate Toxicological Mechanisms
Ford, B. (2019) · eScholarship (California Digital Library)
Kipryushina, Y. O., Maiorova, M. A., & Yakovlev, K. V. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.11.18.469148
Liktor‐Busa, E., Levine, A. A., & Largent‐Milnes, T. M. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-89833-1.00038-0
Li, Z., Zhang, W., He, L., Cui, H., Wang, Y., Wu, X., Zhao, X., Yan, P., Yang, C., Xiao, C., et al. (2023) · Figshare · doi:10.6084/m9.figshare.24136385
Beyond dopamine: exploring endocannabinoids in Parkinson’s disease
Basu, D., Yang, N., Ding, J., Wang, L., Liu, Z., Tang, B., & Cai, H. (2024) · Ageing and Neurodegenerative Diseases · doi:10.20517/and.2024.18
Zhang, L., Zhang, W., He, L., Cui, H., Wang, Y., Wu, X., Zhao, X., Yan, P., Yang, C., Xiao, C., et al. (2023) · Figshare · doi:10.6084/m9.figshare.24136391
Distinct protein profiles in cord blood plasma of children with autism spectrum disorder
Philosoph, L. K., Yoffe, C., Biri, B. E., Baryakh, P., Saar, E. G., Mayorov, M., & Yosef, O. B. (2025) · Scientific Reports · doi:10.1038/s41598-025-29420-5 · Cited by 1
Targeting the endocannabinoid-eicosanoid axis to treat pain: Promise and pitfalls
Gertsch, J. (2026) · Cell chemical biology · doi:10.1016/j.chembiol.2025.12.004
Chen, J., Jiang, S., Chen, Y., Wu, Y., Wang, W., Xie, D., Wei, Y., Yang, Q., Yang, H., Gan, L., et al. (2026) · Aquaculture Reports · doi:10.1016/j.aqrep.2026.103432
van Egmond, N., Jalink, E. A., van der Vliet, D., Henselijn, A. J., Ridder, M. E., Gagestein, B., Stevens, A. F., van Kasteren, S. I., & van der Stelt, M. (2026) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.5c00985
Hong, Y., Chen, X., Cheng, X., Xu, N., Wang, Y., Li, J., Geng, H., Liu, Z., Ying, W., Yang, C., et al. (2026) · npj gut and liver. · doi:10.1038/s44355-026-00062-2
Elgohary, R., & Baraka, S. M. (2026) · Metabolic Brain Disease · doi:10.1007/s11011-026-01862-4
Guo, H., Li, J. S., Gu, C., Liu, N., Sun, J., Wang, D., Meng, S., Geng, D., Lian, Y., Lv, F., et al. (2026) · Journal of Nanobiotechnology · doi:10.1186/s12951-026-04817-0
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Lowrey, P. E., Murtagh, O. L., Gunawardena, M., Pangeni, R., Xu, Q., Jonson, T. O., & Hsu, K. (2026) · Chemical Science · doi:10.1039/d6sc02559e · Cited by 1
Self-citationLysosomal acid lipase regulates cholesterol metabolism during phagosomal maturationPreprint
Saharan, O., Bhawna, B., Saraswati, S. S. K., Akhir, A., Chopra, S., Kumar, D., Mallik, R., & Kamat, S. S. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.09.18.752819
Chandramouli, A., & Kamat, S. S. (2026) · Biochemistry · doi:10.1021/acs.biochem.6c00530
BindingDB (2016) · UC San Diego · doi:10.7270/q2np266b
BindingDB (2021) · UC San Diego · doi:10.7270/q20c508w
BindingDB (2024) · UC San Diego · doi:10.7270/q2st7v2x
BindingDB Entry 50018469: Activity-based protein profiling: Recent advances in medicinal chemistry.
BindingDB (2024) · UC San Diego · doi:10.7270/q23b64bd
BindingDB (2016) · UC San Diego · doi:10.7270/q2n015cw
BindingDB (2020) · UC San Diego · doi:10.7270/q2tx3jbm
Metadata
- Authors
- Hsu, K.-L., Tsuboi, K., Adibekian, A., Pugh, H., Masuda, K., & Cravatt, B. F.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Cravatt, Benjamin F
- Venue
- Nature Chemical Biology
- Published
- 2012-10-28
- Volume
- 8
- Issue
- 12
- Pages
- 999-1007
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- PMC
- PMC3513945
- OpenAlex
- W2134450626
- Cited by
- 222
- References
- 51
- Citations by year
- 2026: 14 · 2025: 7 · 2024: 11 · 2023: 17 · 2022: 17 · 2021: 22 · 2020: 13 · 2019: 15 · 2018: 17 · 2017: 15 · 2016: 22 · 2015: 18 · 2014: 18 · 2013: 15 · 2012: 1
- FWCI
- 12.45
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (U54MH084512, MH-084512)
- National Institute on Drug Abuse (DA033760, P01DA009789, R01DA033760, DA 009789)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- diacylglycerol lipase, 2-arachidonoylglycerol, endocannabinoid system, activity-based probes, macrophage inflammation, eicosanoids, arachidonic acid, cytosolic phospholipase A2, lipopolysaccharide, TNF-α, lipid metabolism, ABHD6
- MeSH terms
- Animals, Arachidonic Acids, Cell Line, Glycerides, Inflammation, Lipoprotein Lipase, Neurons, Prostaglandins, Triazoles, Tumor Necrosis Factor-alpha, Signal Transduction, Cytokines, Arachidonic Acid, Macrophages, Peritoneal, Mice, Knockout, Protein Isoforms, Proteome, Quantitative Structure-Activity Relationship, Lipid Metabolism, Mice, Drug Discovery, Endocannabinoids
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