Stadler Julia T, Lackner Sonja, Mörkl Sabrina, Meier-Allard Nathalie, Scharnagl Hubert, Rani Alankrita, Mangge Harald, Zelzer Sieglinde, Holasek Sandra J, Marsche Gunther
Division of Pharmacology, Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of Graz, Universitätsplatz 4, 8010 Graz, Austria.
Division of Immunology, Otto Loewi Research Center, Medical University of Graz, Heinrichstraße 31a, 8010 Graz, Austria.
Biomedicines. 2022 Apr 13;10(4):895. doi: 10.3390/biomedicines10040895.
Anorexia nervosa (AN) is a severe eating disorder affecting primarily female adolescents and younger adults. The energy deprivation associated with AN has been shown to alter lipoprotein metabolism, which may affect cardiovascular risk. However, the mechanisms leading to alterations in the composition, structure, and function of lipoproteins in AN patients are not well-understood yet. Here, we investigated the lipid abnormalities associated with AN, particularly changes in the distribution, composition, metabolism, and function of lipoprotein subclasses. In this exploratory study, we analyzed serum samples of 18 women diagnosed with AN (BMI < 17.5 kg/m2) and 24 normal-weight women (BMI from 18.5−24.9 kg/m2). Using the Quantimetrix Lipoprint® system, we determined low-density lipoprotein (LDL) subclass distribution, including quantitative measurements of very low-density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and high-density lipoprotein (HDL) subclass distribution. We quantified the most abundant apolipoproteins of HDL and assessed lecithin-cholesterol acyltransferase (LCAT) and cholesteryl-ester transfer protein (CETP) activities. In addition, anti-oxidative capacity of apoB-depleted serum and functional metrics of HDL, including cholesterol efflux capacity and paraoxonase activity were assessed. The atherogenic lipoprotein subclasses VLDL and small LDL particles were increased in AN. Levels of VLDL correlated significantly with CETP activity (rs = 0.432, p = 0.005). AN was accompanied by changes in the content of HDL-associated apolipoproteins involved in triglyceride catabolism, such as apolipoprotein C-II (+24%) and apoA-II (−27%), whereas HDL-associated cholesterol, phospholipids, and triglycerides were not altered. Moreover, AN did not affect HDL subclass distribution, cholesterol efflux capacity, and paraoxonase activity. We observed a shift to more atherogenic lipoprotein subclasses in AN patients, whereas HDL functionality and subclass distribution were not altered. This finding underpins potential detrimental effects of AN on lipid metabolism and the cardiovascular system by increasing atherosclerotic risk factors.
神经性厌食症(AN)是一种主要影响女性青少年和年轻成年人的严重饮食失调症。与AN相关的能量剥夺已被证明会改变脂蛋白代谢,这可能会影响心血管风险。然而,导致AN患者脂蛋白组成、结构和功能改变的机制尚未完全明确。在此,我们研究了与AN相关的脂质异常,特别是脂蛋白亚类的分布、组成、代谢和功能变化。在这项探索性研究中,我们分析了18名被诊断为AN(体重指数<17.5kg/m²)的女性和24名正常体重女性(体重指数为18.5 - 24.9kg/m²)的血清样本。使用Quantimetrix Lipoprint®系统,我们确定了低密度脂蛋白(LDL)亚类分布,包括极低密度脂蛋白(VLDL)、中间密度脂蛋白(IDL)和高密度脂蛋白(HDL)亚类分布的定量测量。我们对HDL中最丰富的载脂蛋白进行了定量,并评估了卵磷脂胆固醇酰基转移酶(LCAT)和胆固醇酯转移蛋白(CETP)的活性。此外,还评估了脱除载脂蛋白B血清的抗氧化能力以及HDL的功能指标,包括胆固醇流出能力和对氧磷酶活性。AN患者中致动脉粥样硬化的脂蛋白亚类VLDL和小LDL颗粒增加。VLDL水平与CETP活性显著相关(rs = 0.432,p = 0.005)。AN伴随着参与甘油三酯分解代谢的HDL相关载脂蛋白含量的变化,例如载脂蛋白C-II(+24%)和载脂蛋白A-II(-27%),而HDL相关的胆固醇、磷脂和甘油三酯没有改变。此外,AN不影响HDL亚类分布、胆固醇流出能力和对氧磷酶活性。我们观察到AN患者向更具致动脉粥样硬化性的脂蛋白亚类转变,而HDL功能和亚类分布未改变。这一发现强调了AN通过增加动脉粥样硬化危险因素对脂质代谢和心血管系统的潜在有害影响。