Dietary linoleic acid-induced alterations in pro- and anti-nociceptive lipid autacoids

Ramsden, Christopher E.; Ringel, Amit; Majchrzak-Hong, Sharon F.; Yang, Jun; Blanchard, H.; Zamora, Daisy; Loewke, James; Rapoport, Stanley I.; Hibbeln, Joseph R.; Davis, John M.; Hammock, Bruce D.; Taha, Ameer Y.

doi:10.1177/1744806916636386

Cited by 46 publications

(55 citation statements)

References 51 publications

(120 reference statements)

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“…We previously demonstrated in rats (11) that increasing dietary linoleic acid markedly increased the abundance of linoleic acid and its oxidized derivatives [for example, hydroxyoctadecadienoates (HODEs)] in tissues associated with idiopathic pain syndromes, including the skin. Moreover, in a trial involving 67 patients with chronic headaches, a linoleic acid–lowering dietary intervention decreased headache pain (12), and decreases in circulating linoleic acid were associated with clinical pain reduction (27), suggesting that linoleic acid or its derivatives could potentially contribute to pain in humans.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously shown in rats that increasing dietary linoleic acid increases linoleic acid derivatives in a dose-dependent manner in many tissues including the skin (11). A small human trial has found correlations between a low–linoleic acid diet intervention and decreased headache pain (12, 13) and between reductions in circulating linoleic acid and pain relief, suggesting that linoleic acid–derived mediators might contribute to sensory signaling.…”

Section: Introductionmentioning

confidence: 99%

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A systems approach for discovering linoleic acid derivatives that potentially mediate pain and itch

et al. 2017

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Chronic pain and itch are common hypersensitivity syndromes that are affected by endogenous mediators. We applied a systems-based, translational approach to predict, discover, and characterize mediators of pain and itch that are regulated by diet and inflammation. Profiling of tissue-specific precursor abundance and biosynthetic gene expression predicted that inflamed skin would be abundant in four previously unknown 11-hydroxy-epoxy-or 11-keto-epoxy-octadecenoate linoleic acid derivatives and four previously identified 9- or 13-hydroxy-epoxy- or 9- or 13-keto-epoxy-octadecenoate linoleic acid derivatives. All of these mediators were confirmed to be abundant in rat and human skin by mass spectrometry. However, only the two 11-hydroxy-epoxy-octadecenoates sensitized rat dorsal root ganglion neurons to release more calcitonin gene–related peptide (CGRP), which is involved in pain transmission, in response to low pH (which mimics an inflammatory state) or capsaicin (which activates ion channels involved in nociception). The two 11-hydroxy-epoxy-octadecenoates share a 3-hydroxy-Z-pentenyl-E-epoxide moiety, thus suggesting that this substructure could mediate nociceptor sensitization. In rats, intradermal hind paw injection of 11-hydroxy-12,13-trans-epoxy-(9Z)-octadecenoate elicited C-fiber–mediated sensitivity to thermal pain. In a randomized trial testing adjunctive strategies to manage refractory chronic headaches, reducing the dietary intake of linoleic acid was associated with decreases in plasma 11-hydroxy-12,13-trans-epoxy-(9Z)-octadecenoate, which correlated with clinical pain reduction. Human psoriatic skin had 30-fold higher 9-keto-12,13-trans-epoxy-(10E)-octadecenoate compared to control skin, and intradermal injection of this compound induced itch-related scratching behavior in mice. Collectively, these findings define a family of endogenous mediators with potential roles in pain and itch.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A systems approach for discovering linoleic acid derivatives that potentially mediate pain and itch

et al. 2017

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“…A recent meta-analysis reported that fried food consumption was associated with hypertension and weight gain 50 . In vivo, the concentration of circulating oxylipins depends on the availability of their precursor fatty acid 10, 11, 51 . However, studies have demonstrated that dietary oxylipins are absorbed 17–20 and incorporated into blood chylomicrons 52 .…”

Section: Discussionmentioning

confidence: 99%

Lipidomic Analysis of Oxidized Fatty Acids in Plant and Algae Oils

Richardson¹,

Hennebelle²,

Otoki

et al. 2017

J. Agric. Food Chem.

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Linoleic acid (LA) and alpha-linolenic acid (ALA) in plant or algae oils are precursors to oxidized fatty acid metabolites known as oxylipins. Liquid chromatography tandem mass spectrometry was used to quantify oxylipins in soybean, corn, olive, canola and four high-oleic acid algae oils at room temperature or after heating for 10 minutes at 100°C. Flaxseed oil oxylipin concentrations were determined in a follow-up experiment that compared it to soybean, canola, corn and olive oil. Published economic disappearance data for soybean, canola, corn and olive oil were used to estimate daily oxylipin intake. The LA and ALA fatty acid composition of the oils was generally related to their respective oxylipin metabolites, except for olive and flaxseed oil which had higher LA-derived mono-hydroxy and ketone oxylipins than other oils, despite their low LA content. Algae oils had the least amount of oxylipins. The change in oxylipin concentrations was not significantly different amongst the oils after short-term heating. Estimated oxylipin intake from non-heated soybean, canola, corn and olive oil was 1.1 mg per person per day. These findings suggest that oils represent a dietary source of LA- and ALA- derived oxylipins and that the response of oils to short-term heating does not differ amongst the various oils.

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“…The low LA diet contained 85.5 % saturated fatty acids, 7.4 % monounsaturated fatty acids, 2.3 % LA, and 4.8 % α-LNA [28] derived from hydrogenated coconut oil (8.73 g/100 g), flaxseed oil (0.77 g/100 g), and olive oil (0.5 g/100 g) [28]. The percent energy provided by LAwas 5.2 % en for the adequate LA diet and 0.4 % en for the low LA diet [36]. …”

Section: Methodsmentioning

confidence: 99%

“…at 250 ng/h), in view of the reported dampening effects of n-6 PUFA deprivation on brain AA metabolism [29, 31]. Rats were fed an adequate LA diet containing 27.6 % LA of total fatty acids (equivalent to 5.2 % energy (en)) or a low LA diet containing 2.3 % LA of total fatty acids (0.4 % en) [36] for 15 weeks, and then infused with LPS (250 ng/h) i.c.v. into the fourth ventricle for 2 days using a mini-osmotic pump.…”

Section: Introductionmentioning

confidence: 99%

Dietary Linoleic Acid Lowering Reduces Lipopolysaccharide-Induced Increase in Brain Arachidonic Acid Metabolism

et al. 2016

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Linoleic acid (LA, 18:2n-6) is a precursor to arachidonic acid (AA, 20:4n-6), which can be converted by brain lipoxygenase and cyclooxygenase (COX) enzymes into various lipid mediators involved in the regulation of brain immunity. Brain AA metabolism is activated in rodents by the bacterial endotoxin, lipopolysaccharide (LPS). This study tested the hypothesis that dietary LA lowering, which limits plasma supply of AA to the brain, reduces LPS-induced upregulation in brain AA metabolism. Male Fischer CDF344 rats fed an adequate LA (5.2 % energy (en)) or low LA (0.4 % en) diet for 15 weeks were infused with LPS (250 ng/h) or vehicle into the fourth ventricle for 2 days using a mini-osmotic pump. The incorporation rate of intravenously infused unesterified 14C-AA into brain lipids, eicosanoids, and activities of phospholipase A2 and COX-1 and 2 enzymes were measured. Dietary LA lowering reduced the LPS-induced increase in prostaglandin E2 concentration and COX-2 activity (P < 0.05 by two-way ANOVA) without altering phospholipase activity. The 14C-AA incorporation rate into brain lipids was decreased by dietary LA lowering (P < 0.05 by two-way ANOVA). The present findings suggest that dietary LA lowering reduced LPS-induced increase in brain markers of AA metabolism. The clinical utility of LA lowering in brain disorders should be explored in future studies.

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Dietary linoleic acid-induced alterations in pro- and anti-nociceptive lipid autacoids

Cited by 46 publications

References 51 publications

A systems approach for discovering linoleic acid derivatives that potentially mediate pain and itch

A systems approach for discovering linoleic acid derivatives that potentially mediate pain and itch

Lipidomic Analysis of Oxidized Fatty Acids in Plant and Algae Oils

Dietary Linoleic Acid Lowering Reduces Lipopolysaccharide-Induced Increase in Brain Arachidonic Acid Metabolism

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