Division of Clinical Chemistry and Biochemistry, Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
Am J Clin Nutr. 2022 Sep 2;116(3):786-797. doi: 10.1093/ajcn/nqac131.
Lipid emulsions are a key component of total parenteral nutrition (TPN) and are administered to patients who are unable to ingest their daily required calories orally. Lipid emulsions rich with n-6 (ω-6) PUFAs are known to cause parenteral nutrition-associated liver disease and have inflammatory side effects, whereas n-3 PUFA-rich emulsions have favourable clinical outcomes.
The present study used targeted lipid mediator analysis to investigate the metabolism of a n-3 PUFA-rich lipid emulsion and a n-6 PUFA-rich lipid emulsion in a mouse model of TPN and in primary human monocyte-derived macrophages (MDMs) and CD4+ T cells.
Mice given n-3 PUFA-based TPN for 7 d had a less proinflammatory lipid mediator profile compared with those receiving n-6 PUFA-based TPN. This was characterized by higher concentrations of specialized pro-resolving mediators (SPMs) and endocannabinoids, including resolvin D (RvD) 1, maresin (MaR) 1, MaR2, protectin D1 (PD1), protectin DX (PDX), and the endocannabinoids eicosapentaenoyl ethanolamide (EPEA) and docosahexaenoyl ethanolamide (DHEA) in the liver and RvD1, 17R-RvD1, RvD2, RvD3, RvD5, MaR1, MaR2, PD1, PDX, and EPEA and DHEA in the spleen. The spleen was identified as a source of high lipid mediator and SPM formation as lipid mediator concentrations were on average 25-fold higher than in the liver. Additionally, n-3 PUFA-treated primary human MDMs produced RvD5 and the endocannabinoids EPEA and DHEA, which was associated with an increased IL-10 secretion. In contrast, primary human CD4+ T cells showed only an increase in SPM precursors and an increase in the endocannabinoids EPEA and DHEA, which was associated with reduced cytokine expression.
This demonstrates that lipid mediators, particularly SPMs and endocannabinoids from spleen, could play a key role in facilitating the favorable clinical outcomes associated with the use of n-3 PUFA-rich lipid emulsions in TPN.
脂肪乳剂是全胃肠外营养（TPN）的一个重要组成部分，用于那些无法经口摄入每日所需热量的患者。富含 n-6（ω-6）多不饱和脂肪酸（PUFA）的脂肪乳剂已知会引起肠外营养相关性肝病，并具有炎症副作用，而富含 n-3 PUFA 的乳剂则具有良好的临床结果。
本研究使用靶向脂质介质分析来研究富含 n-3 PUFA 的脂肪乳剂和富含 n-6 PUFA 的脂肪乳剂在 TPN 小鼠模型和原代人单核细胞衍生的巨噬细胞（MDMs）和 CD4+T 细胞中的代谢。
与接受 n-6 PUFA 为基础的 TPN 的小鼠相比，接受 n-3 PUFA 为基础的 TPN 治疗 7 天的小鼠具有较少的促炎脂质介质谱。这表现为更高浓度的特殊的促解决介质（SPMs）和内源性大麻素，包括 RvD1、maresin（MaR）1、MaR2、保护素 D1（PD1）、保护素 DX（PDX）和内源性大麻素 eicosapentaenoyl 乙醇酰胺（EPEA）和 docosahexaenoyl 乙醇酰胺（DHEA）在肝脏和 RvD1、17R-RvD1、RvD2、RvD3、RvD5、MaR1、MaR2、PD1、PDX、EPEA 和 DHEA 在脾脏中。脾脏被确定为高脂质介质和 SPM 形成的来源，因为脂质介质浓度平均比肝脏高 25 倍。此外，n-3 PUFA 处理的原代人 MDMs 产生 RvD5 和内源性大麻素 EPEA 和 DHEA，这与 IL-10 分泌增加有关。相比之下，原代人 CD4+T 细胞仅显示 SPM 前体增加和内源性大麻素 EPEA 和 DHEA 增加，这与细胞因子表达减少有关。
这表明脂质介质，特别是来自脾脏的 SPMs 和内源性大麻素，可能在促进富含 n-3 PUFA 的脂肪乳剂在 TPN 中使用相关的良好临床结果方面发挥关键作用。
