Jeziorny Krzysztof, Pietrowska Karolina, Sieminska Julia, Zmyslowska-Polakowska Ewa, Kretowski Adam, Ciborowski Michal, Zmyslowska Agnieszka
Department of Endocrinology and Metabolic Diseases, Polish Mother's Memorial Hospital-Research Institute, Lodz, Poland.
Department of Paediatric Endocrinology, Medical University of Lodz, Lodz, Poland.
Front Mol Biosci. 2023 Nov 6;10:1251905. doi: 10.3389/fmolb.2023.1251905. eCollection 2023.
Alström syndrome (ALMS) and Bardet-Biedl syndrome (BBS) are among the so-called ciliopathies and are associated with the development of multiple systemic abnormalities, including early childhood obesity and progressive neurodegeneration. Given the progressive deterioration of patients' quality of life, in the absence of defined causal treatment, it seems reasonable to identify the metabolic background of these diseases and search for their progression markers. The aim of this study was to find metabolites characteristic to ALMS and BBS, correlating with clinical course parameters, and related to the diseases progression. Untargeted metabolomics of serum samples obtained from ALMS and BBS patients (study group; n = 21) and obese/healthy participants (control group; each of 35 participants; n = 70) was performed using LC-QTOF-MS method at the study onset and after 4 years of follow-up. Significant differences in such metabolites as valine, acylcarnitines, sphingomyelins, phosphatidylethanolamines, phosphatidylcholines, as well as lysophosphatidylethanolamines and lysophosphatidylcholines were observed when the study group was compared to both control groups. After a follow-up of the study group, mainly changes in the levels of lysophospholipids and phospholipids (including oxidized phospholipids) were noted. In addition, in case of ALMS/BBS patients, correlations were observed between selected phospholipids and glucose metabolism parameters. We also found correlations of several LPEs with patients' age ( < 0.05), but the level of only one of them (hexacosanoic acid) correlated negatively with age in the ALMS/BBS group, but positively in the other groups. Patients with ALMS/BBS have altered lipid metabolism compared to controls or obese subjects. As the disease progresses, they show elevated levels of lipid oxidation products, which may suggest increased oxidative stress. Selected lipid metabolites may be considered as potential markers of progression of ALMS and BBS syndromes.
阿尔斯特伦综合征（ALMS）和巴德-比德尔综合征（BBS）属于所谓的纤毛病，与多种全身异常的发展有关，包括儿童早期肥胖和进行性神经退行性变。鉴于患者生活质量的逐渐恶化，在缺乏明确病因治疗的情况下，确定这些疾病的代谢背景并寻找其进展标志物似乎是合理的。本研究的目的是找到ALMS和BBS特有的代谢物，与临床病程参数相关，并与疾病进展相关。在研究开始时和随访4年后，使用液相色谱-四极杆飞行时间质谱法对从ALMS和BBS患者（研究组；n = 21）以及肥胖/健康参与者（对照组；每组35名参与者；n = 70）获得的血清样本进行非靶向代谢组学分析。当将研究组与两个对照组进行比较时，观察到缬氨酸、酰基肉碱、鞘磷脂、磷脂酰乙醇胺、磷脂酰胆碱以及溶血磷脂酰乙醇胺和溶血磷脂酰胆碱等代谢物存在显著差异。对研究组进行随访后，主要注意到溶血磷脂和磷脂（包括氧化磷脂）水平的变化。此外，在ALMS/BBS患者中，观察到选定的磷脂与葡萄糖代谢参数之间存在相关性。我们还发现几种溶血磷脂酰乙醇胺与患者年龄相关（P < 0.05），但其中只有一种（二十六烷酸）在ALMS/BBS组中与年龄呈负相关，而在其他组中呈正相关。与对照组或肥胖受试者相比，ALMS/BBS患者的脂质代谢发生了改变。随着疾病进展，他们的脂质氧化产物水平升高，这可能表明氧化应激增加。选定的脂质代谢物可被视为ALMS和BBS综合征进展的潜在标志物。
