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Identification of a Candidate Adropin Receptor
Author(s) -
Stein Lauren,
Samson Willis,
Yosten Gina
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.997.5
Subject(s) - receptor , g protein coupled receptor , orphan receptor , microbiology and biotechnology , biology , gene knockdown , signal transduction , cell culture , cancer research , gene , biochemistry , genetics , transcription factor
Adropin, a peptide secreted by the liver, has been reported to be a novel mediator of energy metabolism. Clinical studies have shown an association between adropin levels and pathological markers of metabolic disease. Our lab has found that intra‐arterial administration of adropin enhances glucose disposal despite decreases in plasma insulin levels in healthy male rats. These data support a role for adropin in the regulation of glucose homeostasis; however, the mechanism has yet to be elucidated, partly due to the elusiveness of the adropin receptor. In endothelial cell cultures adropin stimulated downstream signaling pathways typically associated with G protein coupled receptor (GPCR) activation (Lovren 2010). Therefore, we hypothesized that adropin signals via a GPCR and in particular one of the known ~135 orphan GPCRs. To test this hypothesis, we first identified three adropin responsive cell lines [human gastric carcinoma (KATOIII), human coronary artery endothelial cells (HCAEC) and mouse fibroblasts (3T3‐L1)] using cfos mRNA expression as a reporter of cellular activation. We then applied the “Deductive Ligand‐Receptor Matching Strategy” developed in our lab (Yosten 2012) to generate an orphan GPCR expression profile of each cell line and identified five adropin receptor candidates; GPR151, TAAR9, GPR160, GPR19, and GPR63. In preliminary experiments, knockdown of one of these orphan receptors using siRNA abrogated adropin‐induced cfos mRNA expression in KATOIII cells, identifying this orphan receptor to be our top candidate adropin receptor. Identification of the cognate adropin receptor will facilitate our current attempts to identify the sites and mechanisms of action of this potent, liver‐derived hormone.