Impact of GPR1 signaling on maternal high-fat feeding and placenta metabolism in mice.

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  • Additional Information
    • Source:
      Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901226 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1555 (Electronic) Linking ISSN: 01931849 NLM ISO Abbreviation: Am J Physiol Endocrinol Metab Subsets: MEDLINE
    • Publication Information:
      Original Publication: Bethesda, MD. : American Physiological Society
    • Subject Terms:
      Chemokines/*genetics ; Diabetes, Gestational/*genetics ; Pregnancy/*metabolism ; Receptors, G-Protein-Coupled/*genetics; Adult ; Animals ; Blood Glucose/metabolism ; Cell Proliferation/genetics ; Chemokines/metabolism ; Diabetes, Gestational/metabolism ; Diet, High-Fat ; Fatty Acid-Binding Proteins/metabolism ; Female ; Gene Knockdown Techniques ; Glucose Transporter Type 3/metabolism ; Humans ; Insulin/metabolism ; Insulin-Secreting Cells/cytology ; Intercellular Signaling Peptides and Proteins ; Lipid Metabolism/genetics ; Mice ; Placenta ; Receptors, G-Protein-Coupled/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; 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.
    • Contributed Indexing:
      Keywords: GDM; GLUT-3; GPR1; chemerin; placenta
    • Accession Number:
      0 (Blood Glucose)
      0 (Chemokines)
      0 (Fabp4 protein, mouse)
      0 (Fatty Acid-Binding Proteins)
      0 (GPR1 protein, human)
      0 (GPR1 protein, mouse)
      0 (Glucose Transporter Type 3)
      0 (Insulin)
      0 (Intercellular Signaling Peptides and Proteins)
      0 (RARRES2 protein, human)
      0 (Receptors, G-Protein-Coupled)
      0 (Slc2a3 protein, mouse)
      0 (chemerin protein, mouse)
    • Publication Date:
      Date Created: 20190306 Date Completed: 20200102 Latest Revision: 20210115
    • Publication Date:
      20221213
    • Accession Number:
      10.1152/ajpendo.00437.2018
    • Accession Number:
      30835511