9-PAHSA is an endogenous bioactive lipid from the FAHFAs class [1]. 9-PAHSA modulates GPCR signaling (such as activating GPR40/GPR120 or antagonizing chemokine receptors) and alleviates lipotoxicity and mitochondrial dysfunction in hepatocytes [2-3]. 9-PAHSA is mainly used to study the mechanism of diabetes and ischemia-reperfusion injury [4].
In primary murine hepatocytes (PMH), 9-PAHSA (5-40μM; 24h) treatment improved the viability of the steatotic PMH [5]. In RAW 264.7 cells, 9-PAHSA (2-10μM; 24h) treatment inhibited LPS-stimulated IL-1β and IL-6 gene expression [6].
In db/db mice, 9-PAHSA (50mg/kg; ig; 4weeks) treatment lowered glycemia [7]. In ischemia/reperfusion (I/R) injury mice model, 9-PAHSA (40mg/kg, 80mg/kg; ip; single injection) treatment alleviated myocardial I/R injury [8].
References:
[1]. Pflimlin E, Bielohuby M, Korn M, et al. Acute and repeated treatment with 5-PAHSA or 9-PAHSA isomers does not improve glucose control in mice[J]. Cell metabolism, 2018, 28(2): 217-227. e13.
[2]. Wohlfart P, Chehtane M, Luna E, et al. 9-PAHSA displays a weak anti-inflammatory potential mediated by specific antagonism of chemokine G protein-coupled receptors[J]. Frontiers in Drug Discovery, 2023, 3: 1138461.
[3]. Wang Y M, Liu H X, Fang N Y. 9-PAHSA promotes browning of white fat via activating G-protein-coupled receptor 120 and inhibiting lipopolysaccharide/NF-kappa B pathway[J]. Biochemical and Biophysical Research Communications, 2018, 506(1): 153-160.
[4]. Lupu C, Patel M M, Lupu F. Insights into the functional role of ADTRP (androgen-dependent TFPI-regulating protein) in health and disease[J]. International Journal of Molecular Sciences, 2021, 22(9): 4451.
[5]. Schultz Moreira A R, Rüschenbaum S, Schefczyk S, et al. 9-PAHSA prevents mitochondrial dysfunction and increases the viability of steatotic hepatocytes[J]. International journal of molecular sciences, 2020, 21(21): 8279.
[6]. Dongoran R A, Lin T J, Byekyet A, et al. 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[J]. Biomolecules, 2020, 10(12): 1689.
[7]. Wang Y M, Mi S L, Jin H, et al. 9-PAHSA improves cardiovascular complications by promoting autophagic flux and reducing myocardial hypertrophy in Db/Db mice[J]. Frontiers in pharmacology, 2021, 12: 754387.
[8]. Liu W, Hu J, Wang Y, et al. 9-PAHSA ameliorates microvascular damage during cardiac ischaemia/reperfusion injury by promoting LKB1/AMPK/ULK1-mediated autophagy-dependent STING degradation[J]. Phytomedicine, 2025, 136: 156241.
9-PAHSA是一种内源性生物活性脂质，属于脂肪酸类（FAHFAs） [1]。9-PAHSA能够调节GPCR信号传导（例如激活GPR40/GPR120或拮抗趋化因子受体），并减轻肝细胞的脂毒性和线粒体功能障碍 [2-3]。9-PAHSA主要用于糖尿病和缺血再灌注损伤机制研究 [4]。
在原代小鼠肝细胞（PMH）中，9-PAHSA（5-40μM；24h）处理可提高脂肪变性PMH的活力 [5]。在 RAW 264.7细胞中，9-PAHSA（2-10μM；24h）处理可抑制LPS刺激的IL-1β和IL-6基因表达 [6]。
在db/db小鼠中，9-PAHSA（50mg/kg；ig；4周）治疗可降低血糖 [7]。在缺血/再灌注（I/R）损伤小鼠模型中，9-PAHSA（40mg/kg，80mg/kg；ip；单次注射）治疗可减轻心肌I/R损伤 [8]。