Hepatic chemerin mRNA expression is reduced in human nonalcoholic steatohepatitis

• Published in: European journal of clinical investigation Vol. 47; no. 1; pp. 7 - 18
• Main Authors: Pohl, Rebekka, Haberl, Elisabeth M., Rein‐Fischboeck, Lisa, Zimny, Sebastian, Neumann, Maximilian, Aslanidis, Charalampos, Schacherer, Doris, Krautbauer, Sabrina, Eisinger, Kristina, Weiss, Thomas S., Buechler, Christa
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.01.2017
• Subjects: Adult; Aged; Aged, 80 and over; Blood pressure; Body mass; Body Mass Index; Case-Control Studies; Cell Line; Cells, Cultured; Chemokines - blood; Chemokines - genetics; Chemokines - pharmacology; Comorbidity; Cytokines - metabolism; Diabetes mellitus; Diabetes Mellitus, Type 2 - epidemiology; Fatty liver; Female; FGF21; Fibroblast Growth Factors - metabolism; Fibrosis; Gene expression; Hep G2 Cells; hepatic stellate cells; Hepatic Stellate Cells - drug effects; Hepatic Stellate Cells - metabolism; Hepatocytes; Hepatocytes - drug effects; Hepatocytes - metabolism; Hepcidin; Hepcidins - metabolism; Hip; Humans; Hydrocarbons, Fluorinated - pharmacology; Hypertension; Hypertension - epidemiology; Hypoglycemic Agents - pharmacology; In Vitro Techniques; Insulin; Insulin Resistance; Intercellular Signaling Peptides and Proteins - blood; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - pharmacology; Iron; Leptin - metabolism; Lipocalin; Lipocalin-2 - metabolism; Liver; Liver - metabolism; Liver diseases; Liver X receptors; Liver X Receptors - agonists; Male; Metabolites; Middle Aged; Non-alcoholic Fatty Liver Disease - blood; Non-alcoholic Fatty Liver Disease - epidemiology; Non-alcoholic Fatty Liver Disease - genetics; Patients; Proteins; Real-Time Polymerase Chain Reaction; Receptors, Cytoplasmic and Nuclear - agonists; Recombinant Proteins - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Rosiglitazone; Saturation; Sensitivity analysis; Serum levels; Severity of Illness Index; Steatosis; Stellate cells; Sulfonamides - pharmacology; Thiazolidinediones - pharmacology; Transferrin; Ultrasound; Waist-Hip Ratio; Young Adult; hepatic stellate cells; hepcidin; hepatocytes; FGF21
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1111/eci.12695

Background Chemerin is associated with insulin resistance and is expressed in the liver. Nonalcoholic fatty liver disease (NAFLD) is related to impaired insulin sensitivity, but studies evaluating hepatic and serum chemerin in NAFLD resulted in discordant data. Materials and methods Chemerin mRNA was determined in the liver tissue obtained from 33 controls and 76 NAFLD patients. Chemerin serum levels were measured in a different cohort of patients with ultrasound‐diagnosed NAFLD and the respective controls. Hepatic stellate cells and hepatocytes were exposed to selected metabolites and nuclear receptor agonists to study the regulation of chemerin. Effect of recombinant chemerin on hepatocyte released proteins was analysed. Results Hepatic chemerin expression was not related to BMI, gender, type 2 diabetes and hypertension. Chemerin mRNA did not correlate with steatosis and was negatively associated with inflammation, fibrosis and nonalcoholic steatohepatitis (NASH) score. Patients with NASH had lower chemerin mRNA compared to those with borderline NASH and controls. Factors with a role in NASH mostly did not regulate chemerin in the liver cells. Of note, liver X receptor agonist reduced chemerin protein. Serum chemerin was not changed in NAFLD. Levels positively correlated with age, waist‐to‐hip ratio, systolic blood pressure, serum FGF21 and lipocalin 2, and negatively with transferrin saturation. Chemerin induced FGF21 in supernatants of primary human hepatocytes. Hepcidin, a major regulator of iron homoeostasis and lipocalin 2, were not regulated by chemerin. Conclusion Chemerin mRNA is reduced in the liver of NASH patients, and liver X receptor seems to have a role herein.