1. Impact of GPR1 signaling on maternal high-fat feeding and placenta metabolism in mice
- Author
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Hefei Wang, Wen Zhu, Jianmin Niu, Huashan Zhao, Baobei Wang, Tianxia Xiao, Chen Huang, Binbin Huang, Jie Chen, and Jian Zhang
- Subjects
Adult ,Blood Glucose ,0301 basic medicine ,medicine.medical_specialty ,Physiology ,Placenta ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Diet, High-Fat ,Fatty Acid-Binding Proteins ,Receptors, G-Protein-Coupled ,GPR1 ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Insulin-Secreting Cells ,Physiology (medical) ,Internal medicine ,medicine ,High fat feeding ,Animals ,Humans ,Insulin ,Chemerin ,Receptor ,Cell Proliferation ,Glucose Transporter Type 3 ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,business.industry ,Metabolism ,Lipid Metabolism ,medicine.disease ,Diabetes, Gestational ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Gene Knockdown Techniques ,biology.protein ,Intercellular Signaling Peptides and Proteins ,Female ,Chemokines ,business ,Signal Transduction - Abstract
Chemerin and G protein-coupled receptor 1 (GPR1) are increased in serum and placenta in mice during pregnancy. Interestingly, we observed increased serum chemerin levels and decreased GPR1 expression in placenta of high-fat-diet-fed mice compared with chow-fed mice at gestational day 18. GPR1 protein and gene levels were significantly decreased in gestational diabetes mellitus (GDM) patient placentas. Therefore, we hypothesized that chemerin/GPR1 signaling might participate in the pathogenic mechanism of GDM. We investigated the role of GPR1 in carbohydrate homeostasis during pregnancy using pregnant mice transfected with small interfering RNA for GPR1 or a negative control. GPR1 knockdown exacerbated glucose intolerance, disrupted lipid metabolism, and decreased β-cell proliferation and insulin levels. Glucose transport protein-3 and fatty acid binding protein-4 were downregulated with reducing GPR1 in vivo and in vitro via phosphorylated AKT pathway. Taken together, our findings first demonstrate the expression of GPR1, the characterization of its direct biological effects in humans and mice, as well as the molecular mechanism that indicates the role of GPR1 signaling in maternal metabolism during pregnancy, suggesting a novel feedback mechanism to regulate glucose balance during pregnancy, and GPR1 could be a potential target for the detection and therapy of GDM.
- Published
- 2019