Heni Martin, Hummel Julia, Fritsche Louise, Wagner Robert, Relker Lasse, Machann Jürgen, Schick Fritz, Birkenfeld Andreas L, Schleicher Erwin, Königsrainer Alfred, Häring Hans-Ulrich, Stefan Norbert, Fritsche Andreas, Peter Andreas
Division of Endocrinology and Diabetology, Department of Internal Medicine I, University of Ulm, Ulm, Germany.
Department for Diagnostic Laboratory Medicine, Institute for Clinical Chemistry and Pathobiochemistry, Eberhard Karls University Tübingen, Tübingen, Germany.
Liver Int. 2025 May;45(5):e70046. doi: 10.1111/liv.70046.
While low plasma butyrylcholinesterase (BChE) is a well-established marker of reduced liver synthesis capacity, the clinical significance of elevated BChE is unclear. In small studies, high BChE has long been suspected in hepatic steatosis and metabolic syndrome. We aimed to clarify the relation between BChE, liver fat and glucose metabolism in deeply phenotyped cohorts.
Plasma BChE activity was measured in 844 humans (554 women) of the cross-sectional Tübingen Diabetes Family Study, with a wide BMI range (17.7-55.1 kg/m). It was furthermore measured before and after two independent lifestyle intervention studies in 215 and 116 participants. Liver fat was quantified with H-MR-spectroscopy, and metabolism was assessed by oral glucose tolerance tests.
BChE was positively associated with liver fat, independent of sex, age and BMI. BChE was higher in participants with metabolic syndrome. BChE was positively associated with fasting and 2-h glycaemia, independent of sex, age and BMI. BChE was negatively associated with insulin sensitivity, independent of sex, age, BMI and liver fat. The reduction of liver fat and improvement in insulin sensitivity during lifestyle interventions are associated with the reduction in BChE, independent of body weight loss.
Higher plasma BChE activity is linked to liver fat accumulation, as well as impaired glucose tolerance and insulin resistance, independent of liver fat. This suggests that BChE could be a marker for processes in hepatocytes that contribute to impaired glucose metabolism. Further investigations are needed to clarify the mechanistic contribution and potential diagnostic value of elevated BChE in hepatic steatosis and metabolic diseases.
虽然低血浆丁酰胆碱酯酶（BChE）是肝脏合成能力降低的一个公认标志物，但BChE升高的临床意义尚不清楚。在一些小型研究中，长期以来一直怀疑高BChE与肝脂肪变性和代谢综合征有关。我们旨在阐明在深度表型队列中BChE、肝脏脂肪和葡萄糖代谢之间的关系。
在图宾根糖尿病家族研究的844名人类受试者（554名女性）中测量血浆BChE活性，这些受试者的BMI范围很广（17.7 - 55.1kg/m²）。此外，在两项独立的生活方式干预研究前后，分别对215名和116名参与者进行了测量。用氢磁共振波谱法定量肝脏脂肪，并通过口服葡萄糖耐量试验评估代谢情况。
BChE与肝脏脂肪呈正相关，不受性别、年龄和BMI的影响。代谢综合征患者的BChE较高。BChE与空腹血糖和2小时血糖呈正相关，不受性别、年龄和BMI的影响。BChE与胰岛素敏感性呈负相关，不受性别、年龄、BMI和肝脏脂肪的影响。生活方式干预期间肝脏脂肪的减少和胰岛素敏感性的改善与BChE的降低有关，与体重减轻无关。
较高的血浆BChE活性与肝脏脂肪堆积、葡萄糖耐量受损和胰岛素抵抗有关，与肝脏脂肪无关。这表明BChE可能是肝细胞中导致葡萄糖代谢受损过程的一个标志物。需要进一步研究以阐明BChE升高在肝脂肪变性和代谢疾病中的机制作用及潜在诊断价值。
