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

• Published in: Lipids in health and disease Vol. 22; no. 1; p. 12
• Main Authors: Tan, Lunbo, Ouyang, Zijun, Chen, Zhilong, Sun, Fen, Guo, Haichun, Wang, Feng, Mulder, Monique, Sun, Yuan, Lu, Xifeng, Zhang, Jian V, Danser, A H Jan, Verdonk, Koen, Fan, Xiujun, Yang, Qing
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 25.01.2023; BioMed Central; BMC
• Subjects: Adipocytes; Adipogenesis; Adipokines - metabolism; Adiponectin; Animals; Antibodies; Chemerin; Chemical properties; Chemokines; Chemokines - genetics; Cholesterol; Cholesterol - metabolism; Complications and side effects; Cytokines; Dyslipidemia; Dyslipidemias; Dyslipidemias - genetics; Dyslipidemias - metabolism; Extracellular signal-regulated kinase; Fatty acid-binding protein; Female; Gene expression; Health aspects; High density lipoprotein; Humans; Hypertension; Identification and classification; Laboratory animals; Lipid metabolism; Lipids; Lipoproteins; Low density lipoprotein; Lysophosphatidic acid; Mass spectrometry; Metabolic disorders; Mice; Peroxisome proliferator-activated receptors; Phospholipids; Placenta; Placenta - metabolism; Pre-Eclampsia; Preeclampsia; Pregnancy; Proteins; Risk factors; Scientific imaging; Serum levels; Software; Statistical analysis; Sterol regulatory element-binding protein; Sterols; Triglycerides; Triglycerides - metabolism; Trophoblast; Trophoblasts; Trophoblasts - metabolism; China; Beijing China; Basel Switzerland; United States > US; Switzerland; Japan; Chemerin; Phospholipids; Trophoblast; Placenta; Preeclampsia; Dyslipidemia
• ISSN: 1476-511X; 1476-511X
• DOI: 10.1186/s12944-023-01777-4

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. 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. 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. Overexpression of placental chemerin production disrupts trophoblast lipid metabolism, thereby potentially contributing to dyslipidemia in preeclampsia.