Determination of Major Endogenous FAHFAs in Healthy Human Circulation: The Correlations with Several Circulating Cardiovascular-Related Biomarkers and Anti-Inflammatory Effects on RAW 264.7 Cells

• Main Authors: Rachmad Anres Dongoran, Tsung-Jen Lin, Akhsholphan Byekyet, Sheau-Chung Tang, Jen-Hung Yang, Chin-Hung Liu
• Format: Article
• Language: English
• Published: MDPI AG 2020-12-01
• Series: Biomolecules
• Subjects: FAHFAs; 9-POHSA; 9-OAHSA; cardiovascular disease; anti-inflammatory; SAH
• Online Access: https://www.mdpi.com/2218-273X/10/12/1689

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, <i>S</i>-adenosyl-<span style="font-variant: small-caps;">l</span>-homocysteine (SAH)<i>,</i> and trimethylamine <i>N</i>-oxide (TMAO), but not with <span style="font-variant: small-caps;">l</span>-homocysteine. 9-POHSA was also positively correlated with <span style="font-variant: small-caps;">l</span>-carnitine. Moreover, we confirmed that both 9-POHSA and 9-OAHSA exhibited an anti-inflammatory effect by suppressing LPS stimulated cytokines, including <i>IL-1β</i> and <i>IL-6</i> 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, <span style="font-variant: small-caps;">l</span>-Carnitine elevation, and their anti-inflammatory effects.