Polyunsaturated fatty acids and fatty acid-derived lipid mediators: Recent advances in the understanding of their biosynthesis, structures, and functions

Dyall, Simon C.; Balas, Laurence; Bazán, Nicolás G.; Brenna, J. Thomas; Chiang, Nan; Souza, Felipe da Costa; Dalli, Jesmond; Durand, Thierry; Galano, Jean‐Marie; Lein, Pamela J.; Serhan, Charles N.; Taha, Ameer Y.

doi:10.1016/j.plipres.2022.101165

Cited by 287 publications

(238 citation statements)

References 317 publications

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“…The samples were from 96 White women (n=51 with HBP) and 100 Black women (n=60 with HBP). Oxylipids are signaling lipids that are produced from polyunsaturated fatty acids and regulate inflammation (18). Oxylipids derived from the ARA pathway include prostaglandins, leukotrienes, and hydroxyeicosatetraenoic acids (HETEs) (32).…”

Section: Resultsmentioning

confidence: 99%

Section: Cox and Lox-derived Oxylipids Are Associated With Systolic B...mentioning

confidence: 99%

“…Using untargeted lipidomics and machine learning-assisted predictive modelling, we identified circulating lipids containing arachidonic acid (ARA) as predictive of systolic BP. ARA is an omega-6 fatty acid precursor of bioactive oxygenated lipids (‘oxylipids’), including pro-inflammatory eicosanoids (17, 18). To validate these observations, we performed targeted oxylipid analysis on a subset of MIDUS samples (n=196) and identified oxylipid synthesis pathways that may be differentially active between Black and White women.…”

Section: Introductionmentioning

confidence: 99%

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Identification of novel plasma lipid markers of cardiovascular disease risk in White and Black women

Jain

Davidson

Gonzalez

et al. 2022

Preprint

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Rationale: Cardiovascular disease (CVD) is the leading cause of mortality for women in the USA. Current clinical biomarkers are inadequate to determine CVD risk in women, especially Black women, who disproportionately suffer from CVD. Methods: Clinical data and LC-MS lipidomics from two independent study cohorts were used to identify novel circulating markers of CVD risk in White and Black women. Machine learning assessed predictive efficacy of identified lipids, and targeted oxylipid analysis provided insight into dysregulated inflammatory pathways. Results: Select phospholipids and triglycerides containing acyl chains in the arachidonic acid (ARA) pathway were predictive of systolic blood pressure (BP) after adjusting for biological factors including age, obesity, and glycemic status in White and Black women. Oxylipid levels indicated increased conversion of ARA through the COX and LOX enzymes to pro-inflammatory cytokines in Black women. Conclusion: ARA-containing phospholipid are independent predictors of CVD risk in White and Black women. Predisposition to CVD risk in Black women may further be explained by increased production of pro-inflammatory oxylipids relative to White women, regardless of blood pressure status. Future studies investigating the clinical utility of phospholipid ARA abundance as a marker of CVD risk in White and Black women are warranted.

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Section: Resultsmentioning

confidence: 99%

Section: Cox and Lox-derived Oxylipids Are Associated With Systolic B...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification of novel plasma lipid markers of cardiovascular disease risk in White and Black women

Jain

Davidson

Gonzalez

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…Eicosanoids derived from ϖ-3 fatty acids (i.e., EPA and DHA) have remarkable pro-resolution and(or) anti-inflammatory effects compared to AA-derived pro-inflammatory eicosanoids [ 96 ]. EPA is the precursor of the E-series resolvins (RvE1), while DHA is metabolized to produce D-series resolvins (RvD1 and RvD2), protectins (PD1) and maresins (MaR1) through the activities of Cytochrome P450, COX-2, 5-LOX, 15-LOX and 12-LOX [ 97 ]. The levels of these molecules are lower in the entorhinal cortex of AD patients than in age-matched volunteers, which might benefit AD development considering their stimulatory effect on microglia cells to uptake the pro-inflammatory Aβ42 [ 98 ].…”

Section: Modifiable Proinflammatory Lipid Mediators In Admentioning

confidence: 99%

Modifiable Innate Biology within the Gut–Brain Axis for Alzheimer’s Disease

et al. 2022

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Alzheimer’s disease (AD) is a prototypical inflammation-associated loss of cognitive function, with approximately 90% of the AD burden associated with invading myeloid cells controlling the function of the resident microglia. This indicates that the immune microenvironment has a pivotal role in the pathogenesis of the disease. Multiple peripheral stimuli, conditioned by complex and varied interactions between signals that stem at the intestinal level and neuroimmune processes, are involved in the progression and severity of AD. Conceivably, the targeting of critical innate immune signals and cells is achievable, influencing immune and metabolic health within the gut–brain axis. Considerable progress has been made, modulating many different metabolic and immune alterations that can drive AD development. However, non-pharmacological strategies targeting immunometabolic processes affecting neuroinflammation in AD treatment remain general and, at this point, are applied to all patients regardless of disease features. Despite these possibilities, improved knowledge of the relative contribution of the different innate immune cells and molecules comprising the chronically inflamed brain network to AD pathogenesis, and elucidation of the network hierarchy, are needed for planning potent preventive and/or therapeutic interventions. Moreover, an integrative perspective addressing transdisciplinary fields can significantly contribute to molecular pathological epidemiology, improving the health and quality of life of AD patients. This review is intended to gather modifiable immunometabolic processes based on their importance in the prevention and management of AD.

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“…Supplementation of long-chain polyunsaturated fatty acids (PUFA) enriched for omega-3 PUFA (n-3) have been shown to exhibit beneficial modulatory effects in a variety of diseases, including aging [ 1 ], Parkinson’s and Alzheimer’s disease, depression, or anxiety in rodent models [ 2 ] and human clinical studies [ 3 , 4 ]. Oxylipins compose a large group of PUFA-derived oxidation-derived metabolites involving a variety of enzymes, including cyclooxygenase (COX)2, lipoxygenases (LOX), P450 enzymes, and soluble epoxide hydroxylase (sEphx2) [ 5 , 6 , 7 ]. These metabolites have been implicated in various processes in health and disease such as pain, oxidative stress, and inflammation [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Norepinephrine Inhibits Lipopolysaccharide-Stimulated TNF-α but Not Oxylipin Induction in n-3/n-6 PUFA-Enriched Cultures of Circumventricular Organs

Pflieger

Wolf

Feldotto

et al. 2022

IJMS

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Sensory circumventricular organs (sCVOs) are pivotal brain structures involved in immune-to-brain communication with a leaky blood–brain barrier that detect circulating mediators such as lipopolysaccharide (LPS). Here, we aimed to investigate the potential of sCVOs to produce n-3 and n-6 oxylipins after LPS-stimulation. Moreover, we investigated if norepinephrine (NE) co-treatment can alter cytokine- and oxylipin-release. Thus, we stimulated rat primary neuroglial sCVO cultures under n-3- or n-6-enriched conditions with LPS or saline combined with NE or vehicle. Supernatants were assessed for cytokines by bioassays and oxylipins by HPLC-MS/MS. Expression of signaling pathways and enzymes were analyzed by RT-PCR. Tumor necrosis factor (TNF)α bioactivity and signaling, IL-10 expression, and cyclooxygenase (COX)2 were increased, epoxide hydroxylase (Ephx)2 was reduced, and lipoxygenase 15-(LOX) was not changed by LPS stimulation. Moreover, LPS induced increased levels of several n-6-derived oxylipins, including the COX-2 metabolite 15d-prostaglandin-J2 or the Ephx2 metabolite 14,15-DHET. For n-3-derived oxylipins, some were down- and some were upregulated, including 15-LOX-derived neuroprotectin D1 and 18-HEPE, known for their anti-inflammatory potential. While the LPS-induced increase in TNFα levels was significantly reduced by NE, oxylipins were not significantly altered by NE or changes in TNFα levels. In conclusion, LPS-induced oxylipins may play an important functional role in sCVOs for immune-to-brain communication.

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Polyunsaturated fatty acids and fatty acid-derived lipid mediators: Recent advances in the understanding of their biosynthesis, structures, and functions

Cited by 287 publications

References 317 publications

Identification of novel plasma lipid markers of cardiovascular disease risk in White and Black women

Identification of novel plasma lipid markers of cardiovascular disease risk in White and Black women

Modifiable Innate Biology within the Gut–Brain Axis for Alzheimer’s Disease

Norepinephrine Inhibits Lipopolysaccharide-Stimulated TNF-α but Not Oxylipin Induction in n-3/n-6 PUFA-Enriched Cultures of Circumventricular Organs

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