Identification of Apolipoprotein A‐IV Receptor: a Possibility of an Orphan GPCR?

Abstract

Apolipoprotein‐A4 (apoA‐IV) is a 46 kDa protein that participates in many physiological functions including glucose homeostasis, lipid metabolism, and satiation. Thus, apoA‐IV could serve as a potential target candidate for the treatment of obesity, diabetes, and cardiovascular diseases. A previous study showed that apoA‐IV binds to the plasma membrane of human hepatic cells, but the membrane receptor responsible for apoA‐IV binding remains unknown. In addition, apoA‐IV exerts its physiological roles through PI3K/Akt signaling pathway in rat hypothalamus and mouse adipocytes. We therefore hypothesize that apoA‐IV interacts with a G‐protein‐coupled receptor, more specifically an orphan GPCR. To test this hypothesis, we are employing our Deductive Reasoning Strategy to match apoA‐IV with its potential receptors. Human gastric carcinoma cells (KATO III) and human liver hepatocellular carcinoma cells (HEPG2) treated with apoA‐IV exhibited significant increases in c‐FOS mRNA expression as measured by qPCR. In addition, KATO III and HEPG2 cells expressed many of the overlapping orphan GPCRs. These results suggest that an orphan GPCR for apoA‐IV ligand may potentially exist. Testing other cell lines for their responsiveness to apoA‐IV treatment and expression for orphan GPCRs as well as employing siRNA‐mediated knockdown of orphan GPCRs that are expressed by all tested cell lines is being performed to identify a potentially specific orphan GPCR that interacts with apoA‐IV. Identification of apoA‐IV receptor would provide a novel platform for apoA‐IV‐based therapeutics.Support or Funding InformationNational Institute of HealthThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.