Abstract
BACKGROUND: The 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.
METHODS: Serum 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.
RESULTS: Overexpression 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.
CONCLUSIONS: Overexpression of placental chemerin production disrupts trophoblast lipid metabolism, thereby potentially contributing to dyslipidemia in preeclampsia.
| Original language | English |
|---|---|
| Article number | 12 |
| Pages (from-to) | 12 |
| Journal | Lipids in Health and Disease |
| Volume | 22 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 25 Jan 2023 |
Bibliographical note
Funding Information:The authors would like to thank Dr. Shi Xiao at the Guangdong Provincial Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University for his help with phospholipid lipidome analysis.1College of Veterinary Medicine, Hunan Agricultural University, Changsha 410,128, China;2Center for Energy Metabolism and Reproduction, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518,055, China;3Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC, Rotterdam, Netherlands;4Institute of Marine Biomedicine, School of Food and Drug, Shenzhen Polytechnic, Shenzhen 518,055, China;5Changsha Hospital for Maternal and Child Health Care, Changsha 410,007, China;6Department of Obstetrics and Gynecology, Shenzhen Hengsheng Hospital, Shenzhen 518,115, China;7Clinical Research Center, The First Affiliated Hospital of Shantou University Medical College, Shantou 515,041, China.
Funding Information:
This work was supported by grants from Characteristic Innovation Project of Guangdong Provincial Education Department (No. 2019GKTSCX039); School-Level Scientific Research Project of Shenzhen Polytechnic (No. 6021310023 K); the National Natural Science Foundation of China (31972761 and 81830041);Shenzhen Key Laboratory of Metabolism and Cardiovascular Homeostasis (ZDSYS20190902092903237); Shenzhen Municipal Science and Technology Innovation Council (JCYJ20170307171401691). Lunbo Tan and Koen Verdonk are supported by the Stichting Lijf en Leven.
Publisher Copyright:
© 2023, The Author(s).
