Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore, Singapore.
Diabetes Obes Metab. 2024 Aug;26(8):3429-3438. doi: 10.1111/dom.15686. Epub 2024 May 29.
Fatty acid esters of hydroxy fatty acids (FAHFA) are a class of bioactive lipids with anti-inflammatory, antidiabetic and cardioprotective properties. FAHFA hydrolysis into its fatty acid (FA) and hydroxy fatty acid (HFA) constituents can affect the bioavailability of FAHFA and its subsequent biological effects. We aimed to investigate FAHFA levels and FAHFA hydrolysis activity in children with or without obesity, and in adults with or without coronary artery disease (CAD).
Our study cohort included 20 children without obesity, 40 children with obesity, 10 adults without CAD and 28 adults with CAD. We quantitated plasma levels of four families of FAHFA [palmitic acid hydroxy stearic acid (PAHSA), palmitoleic acid hydroxy stearic acid (POHSA), oleic acid hydroxy stearic acid (OAHSA), stearic acid hydroxy stearic acid] and their corresponding FA and HFA constituents using liquid chromatography-tandem mass spectrometry analysis. Surrogate FAHFA hydrolysis activity was estimated as the FA/FAHFA or HFA/FAHFA ratio.
Children with obesity had lower plasma PAHSA (p = .001), OAHSA (p = .006) and total FAHFA (p = .011) levels, and higher surrogate FAHFA hydrolysis activity represented by PA/PAHSA (p = .040) and HSA/OAHSA (p = .025) compared with children without obesity. Adults with CAD and a history of myocardial infarction (MI) had lower POHSA levels (p = .026) and higher PA/PAHSA (p = .041), POA/POHSA (p = .003) and HSA/POHSA (p = .038) compared with those without MI.
Altered FAHFA metabolism is associated with obesity and MI, and inhibition of FAHFA hydrolysis should be studied further as a possible therapeutic strategy in obesity and MI.
羟基脂肪酸的脂肪酸酯（FAHFA）是一类具有抗炎、抗糖尿病和心脏保护作用的生物活性脂质。FAHFA 水解为其脂肪酸（FA）和羟基脂肪酸（HFA）成分会影响 FAHFA 的生物利用度及其随后的生物学效应。我们旨在研究肥胖儿童和非肥胖儿童以及无冠心病（CAD）和有 CAD 的成年人中 FAHFA 水平和 FAHFA 水解活性。
我们的研究队列包括 20 名无肥胖的儿童、40 名肥胖的儿童、10 名无 CAD 的成年人和 28 名有 CAD 的成年人。我们使用液相色谱-串联质谱分析定量了四种 FAHFA 家族[棕榈酸羟基硬脂酸（PAHSA）、棕榈油酸羟基硬脂酸（POHSA）、油酸羟基硬脂酸（OAHSA）、硬脂酸羟基硬脂酸]及其相应的 FA 和 HFA 成分的血浆水平。替代 FAHFA 水解活性估计为 FA/FAHFA 或 HFA/FAHFA 比值。
肥胖儿童的血浆 PAHSA（p = .001）、OAHSA（p = .006）和总 FAHFA（p = .011）水平较低，PA/PAHSA（p = .040）和 HSA/OAHSA（p = .025）的替代 FAHFA 水解活性较高，与无肥胖的儿童相比。有 CAD 和心肌梗死（MI）病史的成年人的 POHSA 水平较低（p = .026），PA/PAHSA（p = .041）、POA/POHSA（p = .003）和 HSA/POHSA（p = .038）的水平较高，与无 MI 的成年人相比。
FAHFA 代谢的改变与肥胖和 MI 有关，进一步研究 FAHFA 水解的抑制作用可能是肥胖和 MI 的一种潜在治疗策略。
