Various fatty acyl lipid mediators are derived from dietary polyunsaturated fatty acids (PUFAs) and modulate nociception. The modern diet is rich in linoleic acid, which is associated with nociceptive hypersensitivities and may present a risk factor for developing pain conditions. Although recommendations about fatty acid intake exist for some diseases (e.g. cardiovascular disease), the role of dietary fatty acids in promoting pain disorders is not completely understood. To determine how dietary linoleic acid content influences the accumulation of pro- and anti-nociceptive fatty acyl lipid mediators, we created novel rodent diets using custom triglyceride blends rich in either linoleic acid or oleic acid. We quantified the fatty acyl lipidome in plasma of male and female rats fed these custom diets from the time of weaning through nine weeks of age. Dietary fatty acid composition determined circulating plasma fatty acyl lipidome content. Exposure to a diet rich in linoleic acid was associated with accumulation of linoleic and arachidonic acid-derived pro-nociceptive lipid mediators and reduction of anti-nociceptive lipid mediators derived from the omega-3 PUFAs. Our findings provide mechanistic insights into exaggerated nociceptive hypersensitivity associated with excessive dietary linoleic acid intake and highlight potential biomarkers for pain risk stratification.

各种脂肪酰脂质介质源自膳食多不饱和脂肪酸 (PUFA)，可调节伤害感受。现代饮食富含亚油酸，它与伤害性超敏反应有关，可能是发生疼痛的危险因素。尽管针对某些疾病（例如心血管疾病）存在有关脂肪酸摄入量的建议，但膳食脂肪酸在促进疼痛疾病中的作用尚不完全清楚。为了确定膳食亚油酸含量如何影响促伤害性和抗伤害性脂肪酰脂质介质的积累，我们使用富含亚油酸或油酸的定制甘油三酯混合物创建了新型啮齿动物饮食。我们对从断奶到九周龄期间喂食这些定制饮食的雄性和雌性大鼠血浆中的脂肪酰脂质组进行了定量。膳食脂肪酸组成决定了循环血浆脂肪酰脂质组含量。摄入富含亚油酸的饮食与亚油酸和花生四烯酸衍生的促伤害性脂质介质的积累以及源自 omega-3 PUFA 的抗伤害性脂质介质的减少有关。我们的研究结果为与过量膳食亚油酸摄入相关的过度伤害性超敏反应提供了机制见解，并强调了疼痛风险分层的潜在生物标志物。