过氧化物酶体增殖物激活受体 A/G 重编程与巨噬细胞脂质积累相关的代谢。
Peroxisome proliferator-activated receptor A/G reprogrammes metabolism associated with lipid accumulation in macrophages.
机构信息
Center for Excellence in Regional Atmospheric Environment, Institute of Urban Environment, Chinese Academy of Sciences, 1799 Jimei Road, Xiamen, 361021, China.
Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, 1799 Jimei Road, Xiamen, 361021, China.
出版信息
Metabolomics. 2019 Mar 4;15(3):36. doi: 10.1007/s11306-019-1485-6.
INTRODUCTION
Macrophage metabolism contributes to the progression of metabolic diseases, and peroxisome proliferator-activated receptors (PPARs) play vital roles in macrophage metabolism and the treatment of metabolic diseases. However, the role of PPARs in metabolic reprogramming related to lipid accumulation in macrophages, a key pathological event in metabolic diseases, remains unclear.
OBJECTIVES
We aimed to identify PPAR-mediated metabolic reprogramming and potential therapeutic targets associated with lipid accumulation in macrophages.
METHODS
Following treatment with oleate, oleate + WY-14643 and oleate + pioglitazone to induce alterations in PPAR signaling, lipids and relevant metabolism, macrophage samples were analyzed employing an untargeted metabolomics based on gas chromatography-mass spectrometry.
RESULTS
The metabolomics approach revealed that multiple metabolic pathways were altered during lipid accumulation in oleate-treated macrophages and responsive to WY-14643 and pioglitazone treatment. Notably, levels of most metabolites involved in amino acid metabolism and nucleotide metabolism were accumulated in oleate-treated macrophages, and these effects were alleviated or abolished by PPARA/G activation. Additionally, during oleate-induced lipid accumulation and lipid lowering with WY-14643 and pioglitazone in macrophages, levels of most amino acids were positively associated with neutral lipid, total cholesterol, cholesterol ester, total free fatty acid and triglyceride levels but negatively associated with expression of genes related to PPARA/G signaling. Furthermore, glycine was found to be a potential biomarker for assessing lipid accumulation and the lipid-lowering effects of PPARA/G in oleate-treated macrophages.
CONCLUSION
The results of this study revealed a high correlation of amino acid metabolism with lipid accumulation and the lipid-lowering effects of PPARA/G in macrophages.
简介
巨噬细胞代谢促进代谢疾病的进展，过氧化物酶体增殖物激活受体 (PPARs) 在巨噬细胞代谢和代谢疾病治疗中发挥重要作用。然而，PPARs 在与代谢疾病中关键病理事件——巨噬细胞脂质积累相关的代谢重编程中的作用尚不清楚。
目的
我们旨在确定 PPAR 介导的代谢重编程以及与巨噬细胞脂质积累相关的潜在治疗靶点。
方法
用油酸盐、油酸盐+WY-14643 和油酸盐+吡格列酮处理诱导 PPAR 信号转导、脂质和相关代谢改变后，采用基于气相色谱-质谱的非靶向代谢组学方法分析巨噬细胞样本。
结果
代谢组学方法表明，在油酸盐处理的巨噬细胞中脂质积累过程中改变了多种代谢途径，并对 WY-14643 和吡格列酮处理有反应。值得注意的是，参与氨基酸代谢和核苷酸代谢的大多数代谢物的水平在油酸盐处理的巨噬细胞中积累，这些影响通过 PPARA/G 激活得到缓解或消除。此外，在巨噬细胞中油酸盐诱导的脂质积累以及用 WY-14643 和吡格列酮降低脂质时，大多数氨基酸的水平与中性脂质、总胆固醇、胆固醇酯、总游离脂肪酸和甘油三酯水平呈正相关，但与与 PPARA/G 信号转导相关的基因表达呈负相关。此外，发现甘氨酸是评估 PPARA/G 处理的巨噬细胞中脂质积累和脂质降低效果的潜在生物标志物。
结论
本研究结果表明，氨基酸代谢与巨噬细胞中的脂质积累和 PPARA/G 的降脂作用高度相关。
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