College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology & College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China.
Life Sci. 2021 Aug 1;278:119530. doi: 10.1016/j.lfs.2021.119530. Epub 2021 Apr 20.
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.
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.
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.
It implied the existence of negative feed-back regulation and further confirmed the involvement of chemerin in hepatic lipid metabolism.
Chemerin 在肥胖症和代谢综合征患者中含量丰富，可能是由于其在脂肪生成和葡萄糖不耐受中的激活作用。有报道称，血清 chemerin 与脂肪肝呈正相关，但潜在机制知之甚少。我们的目的是研究 chemerin 在肝脂质代谢中的作用。
用油红 O 染色和 TG 定量测定法检测细胞内脂质积累。应用 PCR、QPCR 和 Western blot 检测脂质代谢相关基因、CMKLR1、GPR1 和炎症标记基因。采用荧光素酶报告基因检测法揭示 SREBP1c 对 CMKLR1 和 GPR1 近端启动子活性的下调作用。采用抗体中和试验研究 chemerin 对肝脂质合成的影响。
在人肝癌细胞系 HepG2 中，过表达 chemerin 导致被动脂质积累。chemerin 的失活形式（chemerin 21-158）和活性形式（chemerin 21-157）对 HepG2 细胞的脂质代谢有很强的影响。CMKLR1 或 G 蛋白偶联受体 1（GPR1）的异源表达在肝细胞脂质代谢中发挥与 chemerin 相似的作用。chemerin 通过 HepG2 细胞中的 GPR1 发挥其对脂质代谢的作用。此外，游离脂肪酸和高浓度胰岛素抑制 chemerin 的表达。同样，关键的脂生成转录因子固醇调节元件结合蛋白 1c 抑制 chemerin mRNA 表达和 CMKLR1 和 GPR1 的近端启动子活性。
这暗示了负反馈调节的存在，并进一步证实了 chemerin 参与肝脂质代谢。
