Regulation of Serum Sphingolipids in Andean Children Born and Living at High Altitude (3775 m)

Recent studies on Andean children indicate a prevalence of dyslipidemia and hypertension compared to dwellers at lower altitudes, suggesting that despite similar food intake and daily activities, they undergo different metabolic adaptations. In the present study, the sphingolipid pattern was investigated in serum of 7 underweight (UW), 30 normal weight (NW), 13 overweight (OW), and 9 obese (O) Andean children by liquid chromatography-mass spectrometry (LC-MS). Results indicate that levels of Ceramides (Cers) and sphingomyelins (SMs) correlate positively with biochemical parameters (except for Cers and Vitamin D, which correlate negatively), whereas sphingosine-1-phosphate (S1P) correlates negatively. Correlation results and LC-MS data identify the axis high density lipoprotein-cholesterol (HDL-C), Cers, and S1P as related to hypoxia adaptation. Specifically UW children are characterized by increased levels of S1P compared to O and lower levels of Cers compared to NW children. Furthermore, O children show lower levels of S1P and similar levels of Cers and SMs as NW. In conclusion, our results indicate that S1P is the primary target of hypoxia adaptation in Andean children, and its levels are associated with hypoxia tolerance. Furthermore, S1P can act as marker of increased risk of metabolic syndrome and cardiac dysfunction in young Andeans living at altitude现有针对安第斯儿童的研究显示，与低海拔地区居民相比，该群体的血脂异常（dyslipidemia）与高血压（hypertension）患病率更高，这表明尽管饮食摄入与日常活动水平相近，安第斯儿童却呈现出不同的代谢适应模式。本研究采用液相色谱-质谱联用法（LC-MS），对7名体重过低（UW）、30名体重正常（NW）、13名超重（OW）及9名肥胖（O）的安第斯儿童的血清鞘脂（sphingolipid）谱进行了分析检测。研究结果显示，神经酰胺（Cers）与鞘磷脂（SMs）的水平与多数生化指标呈正相关（仅神经酰胺与维生素D呈负相关），而1-磷酸鞘氨醇（S1P）的水平则与生化指标呈负相关。相关性分析结果与LC-MS数据表明，高密度脂蛋白胆固醇（HDL-C）、神经酰胺与1-磷酸鞘氨醇构成的调控轴与低氧适应密切相关。具体而言，体重过低组儿童的1-磷酸鞘氨醇水平高于肥胖组，且神经酰胺水平低于体重正常组儿童。此外，肥胖组儿童的1-磷酸鞘氨醇水平更低，其神经酰胺与鞘磷脂水平与体重正常组无显著差异。综上，本研究结果表明，1-磷酸鞘氨醇是安第斯儿童低氧适应的核心靶点，其水平与低氧耐受能力相关。此外，1-磷酸鞘氨醇可作为高海拔年轻安第斯人群代谢综合征与心功能异常风险升高的潜在生物标志物。