Autor:innen:
M. Heni (Tübingen, DE)
J. Hummel (Tübingen, DE)
L. Fritsche (Tübingen, DE)
R. Wagner (Tübingen, DE)
L. Relker (Tübingen, DE)
J. Machann (Tübingen, DE)
F. Schick (Tübingen, DE)
A. Birkenfeld (Tübingen, DE)
H. Häring (Tübingen, DE)
N. Stefan (Tübingen, DE)
A. Fritsche (Tübingen, DE)
A. Peter (Tübingen, DE)
Aims
While low plasma cholinesterase activity (CHE) is a well-established marker of reduced hepatic synthesis capacity, the clinical significance of elevated activity is not clear. High CHE was long suspected to be present in hepatic steatosis and metabolic syndrome, as reported by older and smaller studies. We aimed to clarify the relation between CHE and the metabolic syndrome as well as with precisely quantified liver fat content.
Materials and Methods
CHE activity was measured photometrically (Butyrylthiocholin 5-Thio-2-nitrobenzoat) in lithium-heparin plasma in 844 humans (554 women) of the cross-sectional Tübingen Diabetes Family Study with a wide BMI range (17.6 – 55.1 kg/m2) and without severe diseases (including liver diseases). It was furthermore retrospectively measured in 108 participants of the Tübingen Lifestyle Intervention Program (TULIP) before and after a 9-month lifestyle intervention.
Liver fat content was quantified with MR-spectroscopy. All participants underwent detailed metabolic phenotyping including a 2-h 75 g oGTT with glucose, insulin and C-peptide measurements at every 30 minutes. From that, insulin sensitivity was assessed using the Matsuda formula and insulin secretion was estimated as the AUC0-30 of insulin / AUC0-30 of glucose.
Results
CHE was positively associated with liver fat content, independent of sex, age and BMI (p < 0.0001). CHE activity was higher in participants fulfilling the IDF-criteria for the metabolic syndrome (p < 0.0001).
CHE was also positively associated with the fasting plasma glucose and glucose during the OGTT (AUCglucose), independent of sex, age and BMI (both p< 0.0001). While CHE was not associated with insulin secretion (p=0.7, adj. sex, age, insulin sensitivity), it was negatively associated with insulin sensitivity, independent of sex, age and BMI (p < 0.0001), as well as after additional adjustment for liver fat content (p < 0.0001).
The reduction of liver fat content during lifestyle intervention was associated with a reduction in CHE, independent of body weight loss (p < 0.0001). The change in CHE was furthermore associated with the improvement in insulin sensitivity (p < 0.0001). This remained significant even after adjustment for sex, age, BMI and liver fat (p=0.01).
Conclusion
Our cross-sectional and longitudinal results using state-of-the-art approaches for metabolic phenotyping confirm that higher CHE is a marker for liver fat accumulation and is present in patients with metabolic syndrome. We furthermore detected links to glucose tolerance and insulin sensitivity. Of note, these were independent of liver fat content. This suggests that CHE could be not just a marker for liver steatosis but could be indicative of processes in hepatocytes that contribute to metabolic health. Further investigations are needed to clarify the mechanistic contribution and potential diagnostic value of elevated CHE in hepatic steatosis and metabolic diseases.