Table_1_Alcohol Intake Is Associated With Elevated Serum Levels of Selenium and Selenoprotein P in Humans.docx

Selenoprotein P is a hepatokine with antioxidative properties that eliminate a physiologic burst of reactive oxygen species required for intracellular signal transduction. Serum levels of selenoprotein P are elevated during aging and in people with type 2 diabetes, non-alcoholic fatty liver disease, and hepatitis C. However, how serum levels of full-length selenoprotein P are regulated largely remains unknown, especially in the general population. To understand the significance of serum selenoprotein P levels in the general population, we evaluated intrinsic and environmental factors associated with serum levels of full-length selenoprotein P in 1,183 subjects participating in the Shika-health checkup cohort. Serum levels of selenium were positively correlated with liver enzymes and alcohol intake and negatively correlated with body mass index. Serum levels of selenoprotein P were positively correlated with age, liver enzymes, and alcohol intake. In multiple regression analyses, alcohol intake was positively correlated with serum levels of both selenium and selenoprotein P independently of age, gender, liver enzymes, and fatty liver on ultrasonography. In conclusion, alcohol intake is associated with elevated serum levels of selenium and selenoprotein P independently of liver enzyme levels and liver fat in the general population. Moderate alcohol intake may exert beneficial or harmful effects on health, at least partly by upregulating selenoprotein P. These findings increase our understanding of alcohol-mediated redox regulation and form the basis for the adoption of appropriate drinking guidelines.

硒蛋白P（Selenoprotein P）是一种具有抗氧化特性的肝因子，可清除细胞内信号转导所需的生理性活性氧（reactive oxygen species）爆发。血清硒蛋白P水平在衰老过程中升高，在2型糖尿病、非酒精性脂肪肝病及丙型肝炎患者群体中同样升高。然而，全长硒蛋白P的血清水平调控机制目前仍未完全阐明，尤其在普通人群中。为明确普通人群血清硒蛋白P水平的临床意义，本研究针对参与志贺健康检查队列（Shika-health checkup cohort）的1183名受试者，分析了与全长硒蛋白P血清水平相关的内在与环境影响因素。研究发现，血清硒水平与肝酶指标及酒精摄入量呈正相关，与体质量指数呈负相关；血清硒蛋白P水平则与年龄、肝酶指标及酒精摄入量呈正相关。经多元回归分析校正年龄、性别、肝酶指标及超声检查确诊的脂肪肝后，酒精摄入量仍与血清硒及硒蛋白P水平呈独立正相关。综上，在普通人群中，酒精摄入量与血清硒及硒蛋白P水平升高呈独立相关，且不受肝酶水平与肝脏脂肪含量的影响。适量饮酒可能至少部分通过上调硒蛋白P表达，对健康产生双向影响（有益或有害）。本研究结果加深了学界对酒精介导的氧化还原调控机制的理解，可为制定合理饮酒指南提供理论依据。