Functional Metabolomics Reveals Novel Active Products in the DHA Metabolome
Open accessAbstract
Endogenous mechanisms for successful resolution of an acute inflammatory response and the local return to homeostasis are of interest because excessive inflammation underlies many human diseases. In this review, we provide an update and overview of functional metabolomics that identified a new bioactive metabolome of docosahexaenoic acid (DHA). Systematic studies revealed that DHA was converted to DHEA-derived novel bioactive products as well as aspirin-triggered forms of protectins (AT-PD1). The new oxygenated DHEA-derived products blocked PMN chemotaxis, reduced P-selectin expression and platelet-leukocyte adhesion, and showed organ protection in ischemia/reperfusion injury. These products activated cannabinoid receptor (CB2 receptor) and not CB1 receptors. The AT-PD1 reduced neutrophil (PMN) recruitment in murine peritonitis. With human cells, AT-PD1 decreased transendothelial PMN migration as well as enhanced efferocytosis of apoptotic human PMN by macrophages. The recent findings reviewed here indicate that DHEA oxidative metabolism and aspirin-triggered conversion of DHA produce potent novel molecules with anti-inflammatory and organ-protective properties, opening the DHA metabolome functional roles.
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When the anti-inflammatory phase is successful, inflammation resolves slowly over months, promoted at least in part by lipid-derived mediators.
“When this phase is successful, inflammation has been shown to resolve slowly in the course of months, promoted at least in part by lipid‐derived mediators.11”
From Hypoalbuminemia: Pathogenesis and Clinical Significance (2019) · cites this paper as [11]
The section “The Neutrophil (PMN) in Resolution and the Programmed Outcome of Acute Inflammation” says that successful resolution is an active process and that lipid mediators help control inflammation’s duration. It does not say that successful inflammation resolves slowly over months; that timescale is unsupported. (LLM, conf=0.88)
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References 58 · Cited by 52
- Authors
- Shinohara, M., Mirakaj, V., & Serhan, C. N.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Serhan, Charles N.
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2012
- Volume
- 3
- Pages
- 81-81
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC3342038
- OpenAlex
- W1992530514
- Cited by
- 52
- References
- 58
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 4 · 2021: 5 · 2020: 1 · 2019: 4 · 2018: 7 · 2017: 6 · 2016: 2 · 2015: 6 · 2014: 4 · 2013: 6 · 2012: 1
- FWCI
- 5.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Frontiers in Immunology (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Heart, Lung, and Blood Institute (P01HL108801)
- National Institute of General Medical Sciences (R01GM038765)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Keywords
- docosahexaenoic acid, anti-inflammatory metabolites, CB2 receptor, neutrophil chemotaxis, P-selectin, ischemia-reperfusion injury, peritonitis, efferocytosis, oxidative metabolism
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