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Heni, M. ; Hummel, J.* ; Fritsche, L. ; Wagner, R. ; Relker, L.* ; Machann, J. ; Schick, F. ; Birkenfeld, A.L. ; Schleicher, E. ; Königsrainer, A.* ; Häring, H.-U. ; Stefan, N. ; Fritsche, A. ; Peter, A.

Elevated cholinesterase activity and the metabolic syndrome-dissecting fatty liver, insulin resistance and dysglycaemia.

Liver Int. 45:e70046 (2025)

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BACKGROUND AND AIMS: 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. METHODS: 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/m²). It was furthermore measured before and after two independent lifestyle intervention studies in 215 and 116 participants. Liver fat was quantified with ¹H-MR-spectroscopy, and metabolism was assessed by oral glucose tolerance tests. RESULTS: 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. CONCLUSIONS: 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.

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