Increased hepatic Chemerin and CMKLR1 gene expression in human nonalcoholic fatty liver disease

S Döcke; J Lock; S Hoppe; A Rieger; S Florian; MA Osterhoff; P Neuhaus; M Möhlig; MO Weickert; M Stockmann; AFH Pfeiffer; C von Loeffelholz

doi:10.1055/s-0032-1330797

Experimental and Clinical Endocrinology & Diabetes, Inhaltsverzeichnis

Increased hepatic Chemerin and CMKLR1 gene expression in human nonalcoholic fatty liver disease

S Döcke ¹, J Lock ², S Hoppe ², A Rieger ³, S Florian ⁴, MA Osterhoff ¹^,⁵, P Neuhaus ², M Möhlig ⁵, MO Weickert ¹^,⁶, M Stockmann ², AFH Pfeiffer ¹^,⁵, C von Loeffelholz ¹^,⁷

¹Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
²Department of General, Visceral and Transplantation Surgery, Charité – Universitätsmedizin, Berlin, Germany
³Institute of Pathology, Charité – Universitätsmedizin, Berlin, Germany
⁴Department of Nutritional Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
⁵Department of Endocrinology, Diabetes, and Nutrition, Charité – Universitätsmedizin,Berlin, Germany
⁶Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire, CV2 2DX, Coventry, UK, and Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, CV4 7AL, Coventry, UK
⁷Department of Anesthesiology and Intensive Care, University-Medicine Jena, Jena Germany

Abstract

Objective: Inflammatory states of non-alcoholic fatty liver disease (NAFLD) are associated with obesity via adipocytokines. Circulating levels of the adipocytokine chemerin are in vivo associated with NAFLD and hepatic cirrhosis. However, hepatic gene transcription of chemerin and its receptor CMKLR1 are rarely studied, especially in human NAFLD.

Methods: Therefore we conducted a cross-sectional study in which liver tissue was taken intrasurgically from n=47 subjects and graded histologically by an expert pathologist according to the NAFLD activity score (NAS). Hepatic chemerin and CMKLR1 transcription levels were measured via quantitative real-time PCR. Serum chemerin, clinical chemistry and anthropometry were determined additionally.

Results: Hepatic chemerin gene transcription showed a correlation with BMI (R² =0.296, P=0.039), waist circumference (R² =0.397, P=0.005) and percent body fat (R² =0.378, P=0.008). For the chemerin receptor CMKLR1 this was also true for waist circumference (R² =0.369, P=0.010) and percent body fat (R² =0.539, P<0.001). Obese subjects (BMI≥30kg/m²) had higher hepatic chemerin and CMKLR1 mRNA levels compared to normal weight ones (BMI≤25kg/m²; P<0.05). Chemerin and CMKLR1 gene expression correlated with the NAS (R² =0.351, P=0.016; R² =0.296, P=0.043; resp.) and their hepatic mRNA levels were higher in patients with a NAS≥4 compared to lower grades (P<0.05). However, by using linear regression analysis to confirm the influence of the single features of the NAS only lobular inflammation and hepatocyte ballooning but not steatosis were sustained to predict hepatic chemerin mRNA levels.

Conclusion: Our data suggest a role of chemerin/CMKLR1 signalling in human liver affected by inflammatory processes.