油酸诱导巨噬细胞磷脂代谢紊乱的代谢组学研究。
Metabolomics Insights into Oleate-Induced Disorders of Phospholipid Metabolism in Macrophages.
机构信息
Center for Excellence in Regional Atmospheric Environment, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, China.
Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, China.
出版信息
J Nutr. 2021 Mar 11;151(3):503-512. doi: 10.1093/jn/nxaa411.
BACKGROUND
Diet-induced disordered phospholipid metabolism and disturbed macrophage metabolism contribute to the pathogenesis of metabolic diseases. However, the effects of oleate, a main dietary fatty acid, on macrophage phospholipid metabolism are unclear.
OBJECTIVES
We aimed to discover oleate-induced disorders of macrophage phospholipid metabolism and potential therapeutic targets for treating diet-related metabolic diseases.
METHODS
RAW 264.7 cells were exposed to 65 μg oleate/mL, within the blood concentration range of humans and mice, to trigger disorders of phospholipid metabolism. Meanwhile, WY-14643 and pioglitazone, 2 drugs widely used for treating metabolic diseases, were employed to prevent oleate-induced disorders of macrophage phospholipid metabolism. Subsequently, an untargeted metabolomics approach based on liquid chromatography-mass spectrometry was used to discover relevant metabolic disorders and potential therapeutic targets.
RESULTS
We showed that 196 metabolites involved in phospholipid metabolism were altered upon oleate treatment and interventions of WY-14643 and pioglitazone (P < 0.05, 2-tailed Mann-Whitney U test). Notably, most lysophospholipids were decreased, whereas most phospholipids were increased in oleate-treated macrophages. Phosphatidylethanolamines accumulated most among phospholipids, and their acyl chain polyunsaturation increased in oleate-treated macrophages. Additionally, saturated fatty acids were decreased, whereas polyunsaturated fatty acids were increased in oleate-treated macrophages. Furthermore, changes in phosphatidylglycerols, phosphatidylinositols, cardiolipins, phosphatidates, lysophosphatidylglycerols, and acylcarnitines in oleate-treated macrophages could be attenuated or even abolished by WY-14643 and/or pioglitazone treatment.
CONCLUSIONS
Oleate induced accumulation of various phospholipids, increased acyl chain polyunsaturation of phosphatidylethanolamines, and decreased lysophospholipids in RAW 264.7 macrophages. This study suggests macrophage phospholipid and fatty acid metabolism as potential therapeutic targets for intervening diet-related metabolic diseases.
背景
饮食诱导的磷脂代谢紊乱和巨噬细胞代谢紊乱导致代谢性疾病的发生。然而，油酸作为主要的膳食脂肪酸，其对巨噬细胞磷脂代谢的影响尚不清楚。
目的
本研究旨在发现油酸诱导的巨噬细胞磷脂代谢紊乱及其治疗饮食相关代谢性疾病的潜在治疗靶点。
方法
用油酸（浓度范围为 65μg/ml，相当于人和小鼠血液中的油酸浓度）处理 RAW 264.7 细胞，以诱发磷脂代谢紊乱。同时，采用两种广泛用于治疗代谢性疾病的药物 WY-14643 和吡格列酮来预防油酸诱导的巨噬细胞磷脂代谢紊乱。随后，采用基于液相色谱-质谱的非靶向代谢组学方法来发现相关的代谢紊乱和潜在的治疗靶点。
结果
我们发现，油酸处理及 WY-14643 和吡格列酮干预后，有 196 种参与磷脂代谢的代谢物发生改变（P < 0.05，双尾曼-惠特尼 U 检验）。值得注意的是，油酸处理的巨噬细胞中大多数溶血磷脂减少，而大多数磷脂增加。在油酸处理的巨噬细胞中，磷脂酰乙醇胺积累最多，其酰基链多不饱和性增加。此外，饱和脂肪酸减少，而多不饱和脂肪酸增加。此外，WY-14643 和/或吡格列酮处理可减轻或甚至消除油酸处理的巨噬细胞中磷脂酰甘油、磷脂酰肌醇、心磷脂、磷酸酯、溶血磷脂酰甘油和酰基肉碱的变化。
结论
油酸诱导 RAW 264.7 巨噬细胞中各种磷脂的积累、磷脂酰乙醇胺酰基链多不饱和性的增加和溶血磷脂的减少。本研究提示巨噬细胞磷脂和脂肪酸代谢可能是干预饮食相关代谢性疾病的潜在治疗靶点。
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