Chemerin causes lipid metabolic imbalance and induces passive lipid accumulation in human hepatoma cell line via the receptor GPR1.

Abstract Aims Chemerin is abundant in patients with high body mass index and metabolic syndrome possibly due to its activation in adipogenesis and glucose intolerance. It has reported that sera chemerin is positively associated with fatty liver with little known underlying mechanisms. Our aim is to study the role of chemerin in hepatic lipid metabolism. Main methods Oil Red O staining and TG quantitative assay were used to detect intracellular lipid accumulation. PCR, QPCR and western blot were applied to measure lipid metabolism-related genes, CMKLR1, GPR1 and inflammation marker genes. Luciferase reporter assay was employed to uncover the down-regulation of proximate promoter activities of CMKLR1 and GPR1 by SREBP1c. Antibody neutralization assay was used to address the effects of chemerin on hepatic lipid synthesis. Key findings Over-expression of chemerin led to passive lipid accumulation, in human hepatoma cell line HepG2. The disable form of chemerin (chemerin 21–158) and active chemerin (chemerin 21–157) performed strongly effects on lipid metabolism in HepG2 cells. Heterologous expression of CMKLR1 or G-protein coupled receptor1 (GPR1) played similar roles in hepatocyte lipid metabolism as chemerin. Chemerin exerted its effects on lipid metabolism via GPR1 in HepG2 cells. Furthermore, free fatty acids and high concentration insulin inhibited chemerin expression. Consistently, the key lipogenic transcription factor Sterol regulatory element binding protein 1c suppressed chemerin mRNA expression and proximate promoter activities of CMKLR1 and GPR1. Significance It implied the existence of negative feed-back regulation and further confirmed the involvement of chemerin in hepatic lipid metabolism.