Program in Pharmacology and Toxicology, School of Medicine, Tzu Chi University, Hualien 970004, Taiwan.
Indonesian Food and Drug Authority (Indonesian FDA), Jakarta 10560, Indonesia.
Biomolecules. 2020 Dec 17;10(12):1689. doi: 10.3390/biom10121689.
Fatty acid esters of hydroxy fatty acids (FAHFAs) are newly discovered long-chain fatty acids. However, the major endogenous FAHFAs in healthy human circulation, their correlation with cardiovascular (CV) biomarkers, and their anti-inflammatory effects have not been investigated and remain unclear. In the present study, a total of 57 healthy subjects were recruited. Liquid chromatography-mass spectrometry (LC-MS) was developed for the simultaneous determination of seven FAHFAs, four long-chain fatty acids, and four non-traditional circulating CV-related biomarkers. We found two major types of FAHFAs in healthy human circulation, palmitoleic acid ester of 9-hydroxystearic acid (9-POHSA), and oleic acid ester of 9-hydroxystearic acid (9-OAHSA). Both 9-POHSA and 9-OAHSA had a strong positive correlation with each other and were negatively correlated with fasting blood glucose, -adenosyl-l-homocysteine (SAH) and trimethylamine -oxide (TMAO), but not with l-homocysteine. 9-POHSA was also positively correlated with l-carnitine. Moreover, we confirmed that both 9-POHSA and 9-OAHSA exhibited an anti-inflammatory effect by suppressing LPS stimulated cytokines, including and in RAW 264.7 cells. In addition, palmitoleic acid also had a positive correlation with 9-POHSA and 9-OAHSA. As far as we know, this is the first report showing the major endogenous FAHFAs in healthy subjects and their CV protection potential which might be correlated with SAH and TMAO reduction, l-Carnitine elevation, and their anti-inflammatory effects.
羟基脂肪酸的脂肪酸酯（FAHFAs）是新发现的长链脂肪酸。然而，健康人体循环中的主要内源性 FAHFAs、它们与心血管（CV）生物标志物的相关性以及它们的抗炎作用尚未得到研究，目前尚不清楚。在本研究中，共招募了 57 名健康受试者。建立了液相色谱-质谱（LC-MS）法，用于同时测定七种 FAHFAs、四种长链脂肪酸和四种非传统循环 CV 相关生物标志物。我们在健康人体循环中发现了两种主要类型的 FAHFAs，即棕榈油酸 9-羟基硬脂酸酯（9-POHSA）和油酸 9-羟基硬脂酸酯（9-OAHSA）。9-POHSA 和 9-OAHSA 彼此之间具有很强的正相关性，与空腹血糖、-腺苷基-l-同型半胱氨酸（SAH）和三甲胺氧化物（TMAO）呈负相关，但与 l-同型半胱氨酸无关。9-POHSA 还与 l-肉碱呈正相关。此外，我们通过抑制 LPS 刺激的细胞因子，包括 RAW 264.7 细胞中的 和 ，证实了 9-POHSA 和 9-OAHSA 均具有抗炎作用。此外，棕榈酸也与 9-POHSA 和 9-OAHSA 呈正相关。据我们所知，这是首次报道在健康受试者中主要内源性 FAHFAs 及其潜在的 CV 保护作用，这可能与 SAH 和 TMAO 减少、l-肉碱升高以及它们的抗炎作用有关。
