Méaux Marie-Noëlle, Regnier Maitena, Portefaix Aurélie, Borel Olivier, Alioli Candide, Peyruchaud Olivier, Legrand Mélanie, Bacchetta Justine
INSERM, UMR 1033, Lyon, France.
Centre de Référence des Maladies Rares du Calcium et du Phosphate, filière OSCAR, Lyon, France.
Front Pediatr. 2023 Feb 13;11:1094705. doi: 10.3389/fped.2023.1094705. eCollection 2023.
Autotaxin (ATX) is a secreted enzyme with a lysophospholipase D activity, mainly secreted by adipocytes and widely expressed. Its major function is to convert lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA), an essential bioactive lipid involved in multiple cell processes. The ATX-LPA axis is increasingly studied because of its involvement in numerous pathological conditions, more specifically in inflammatory or neoplastic diseases, and in obesity. Circulating ATX levels gradually increase with the stage of some pathologies, such as liver fibrosis, thus making them a potentially interesting non-invasive marker for fibrosis estimation. Normal circulating levels of ATX have been established in healthy adults, but no data exist at the pediatric age. The aim of our study is to describe the physiological concentrations of circulating ATX levels in healthy teenagers through a secondary analysis of the VITADOS cohort. Our study included 38 teenagers of Caucasian origin (12 males, 26 females). Their median age was 13 years for males and 14 years for females, ranging from Tanner 1 to 5. BMI was at the 25th percentile for males and 54th percentile for females, and median blood pressure was normal. ATX median levels were 1,049 (450-2201) ng/ml. There was no difference in ATX levels between sexes in teenagers, which was in contrast to the male and female differences described in the adult population. ATX levels significantly decreased with age and pubertal status, reaching adult levels at the end of puberty. Our study also suggested positive correlations between ATX levels and blood pressure (BP), lipid metabolism, and bone biomarkers. However, except for LDL cholesterol, these factors were also significantly correlated with age, which might be a confounding factor. Still, a correlation between ATX and diastolic BP was described in obese adult patients. No correlation was found between ATX levels and inflammatory marker C-reactive protein (CRP), Body Mass Index (BMI), and biomarkers of phosphate/calcium metabolism. In conclusion, our study is the first to describe the decline in ATX levels with puberty and the physiological concentrations of ATX levels in healthy teenagers. It will be of utmost importance when performing clinical studies in children with chronic diseases to keep these kinetics in mind, as circulating ATX might become a non-invasive prognostic biomarker in pediatric chronic diseases.
自分泌运动因子(ATX)是一种具有溶血磷脂酶D活性的分泌型酶,主要由脂肪细胞分泌,广泛表达。其主要功能是将溶血磷脂酰胆碱(LPC)转化为溶血磷脂酸(LPA),LPA是一种参与多种细胞过程的重要生物活性脂质。由于ATX-LPA轴参与众多病理状况,尤其是炎症性或肿瘤性疾病以及肥胖症,因此对其研究日益增多。在某些病理状态(如肝纤维化)下,循环中ATX水平会随着疾病阶段逐渐升高,这使其成为一种潜在的用于评估纤维化的有趣的非侵入性标志物。健康成年人的ATX正常循环水平已被确定,但尚无儿童期的数据。我们研究的目的是通过对VITADOS队列的二次分析来描述健康青少年循环中ATX水平的生理浓度。我们的研究纳入了38名高加索裔青少年(12名男性,26名女性)。男性的中位年龄为13岁,女性为14岁,处于坦纳1至5期。男性的BMI处于第25百分位数,女性处于第54百分位数,中位血压正常。ATX的中位水平为1049(450 - 2201)ng/ml。青少年中ATX水平在性别之间无差异,这与成年人群中描述的男女差异形成对比。ATX水平随年龄和青春期状态显著下降,在青春期结束时达到成人水平。我们的研究还表明ATX水平与血压(BP)、脂质代谢和骨生物标志物之间存在正相关。然而,除低密度脂蛋白胆固醇外,这些因素也与年龄显著相关,这可能是一个混杂因素。尽管如此,肥胖成年患者中描述了ATX与舒张压之间的相关性。未发现ATX水平与炎症标志物C反应蛋白(CRP)、体重指数(BMI)以及磷/钙代谢生物标志物之间存在相关性。总之,我们的研究首次描述了ATX水平随青春期下降以及健康青少年中ATX水平的生理浓度。在对患有慢性疾病的儿童进行临床研究时牢记这些动力学情况至关重要,因为循环中的ATX可能成为儿科慢性疾病的一种非侵入性预后生物标志物。