Adipokine chemerin overexpression in trophoblasts leads to dyslipidemia in pregnant mice: implications for preeclampsia

Lipids in Health and Disease

Research

Fen Sun¹  Xiujun Fan¹  Jian V. Zhang¹  Haichun Guo²  Yuan Sun³  Xifeng Lu³  Qing Yang⁴  Zhilong Chen⁵  Lunbo Tan⁶  Feng Wang⁷  Monique Mulder⁸  Koen Verdonk⁸  A. H. Jan Danser⁸  Zijun Ouyang⁹ 

[1] Center for Energy Metabolism and Reproduction, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, 518055, Shenzhen, China;Changsha Hospital for Maternal and Child Health Care, 410007, Changsha, China;Clinical Research Center, The First Affiliated Hospital of Shantou University Medical College, 515041, Shantou, China;College of Veterinary Medicine, Hunan Agricultural University, 410128, Changsha, China;College of Veterinary Medicine, Hunan Agricultural University, 410128, Changsha, China;Center for Energy Metabolism and Reproduction, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, 518055, Shenzhen, China;College of Veterinary Medicine, Hunan Agricultural University, 410128, Changsha, China;Center for Energy Metabolism and Reproduction, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, 518055, Shenzhen, China;Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC, Rotterdam, Netherlands;Department of Obstetrics and Gynecology, Shenzhen Hengsheng Hospital, 518115, Shenzhen, China;Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC, Rotterdam, Netherlands;School of Food and Drug, Shenzhen Polytechnic, Institute of Marine Biomedicine, 518055, Shenzhen, China;

关键词: Chemerin;    Preeclampsia;    Dyslipidemia;    Placenta;    Trophoblast;    Phospholipids;   

DOI  :  10.1186/s12944-023-01777-4

 received in 2022-11-11, accepted in 2023-01-17,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe adipokine chemerin regulates adipogenesis and the metabolic function of both adipocytes and liver. Chemerin is elevated in preeclamptic women, and overexpression of chemerin in placental trophoblasts induces preeclampsia-like symptoms in mice. Preeclampsia is known to be accompanied by dyslipidemia, albeit via unknown mechanisms. Here, we hypothesized that chemerin might be a contributor to dyslipidemia.MethodsSerum lipid fractions as well as lipid-related genes and proteins were determined in pregnant mice with chemerin overexpression in placental trophoblasts and chemerin-overexpressing human trophoblasts. In addition, a phospholipidomics analysis was performed in chemerin-overexpressing trophoblasts.ResultsOverexpression of chemerin in trophoblasts increased the circulating and placental levels of cholesterol rather than triglycerides. It also increased the serum levels of lysophosphatidic acid, high-density lipoprotein cholesterol (HDL-C), and and low-density lipoprotein cholesterol (LDL-C), and induced placental lipid accumulation. Mechanistically, chemerin upregulated the levels of peroxisome proliferator-activated receptor g, fatty acid-binding protein 4, adiponectin, sterol regulatory element-binding protein 1 and 2, and the ratio of phosphorylated extracellular signal-regulated protein kinase (ERK)1/2 / total ERK1/2 in the placenta of mice and human trophoblasts. Furthermore, chemerin overexpression in human trophoblasts increased the production of lysophospholipids and phospholipids, particularly lysophosphatidylethanolamine.ConclusionsOverexpression of placental chemerin production disrupts trophoblast lipid metabolism, thereby potentially contributing to dyslipidemia in preeclampsia.

【 授权许可】

CC BY   
© The Author(s) 2023

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