Apelin Adipocyte Signaling Pathway

The apelin gene is X-linked and is synthesized as a 77 amino acid pre-pro-peptide that is cleaved post-translationally to generate several active forms whose lengths range from 36 to 12 amino acids. These isoforms possess similar functions but display different tissue distribution, potency and receptor binding affinity. Apelin acts as a ligand for the APJ receptor (angiotensin II receptor like-1, AT-1), which is coupled to pertussis toxin (PTX)-sensitive G proteins. The apelin/APJ system plays important and various roles in the physiology and pathophysiology of many organs, including regulation of blood pressure, angiogenesis, cardiac contractility, metabolic balance, cell proliferation and apoptosis. It is noteworthy that the APJ receptor is also activated by APELA, a distinct peptide hormone with significant effects on cardiac development.Apelin is an adipocytokine secreted by, and sensed by, adipocytes, that tends to counteract diabetes mellitus and diabetic complications. It is induced in part by insulin, and, like insulin, by glucose and repletion. Via several pathways such as AMPK, PKA, and ERK1/2, it dampens ROS generation, increases mitochondrial biogenesis, reduces fatty acid generation and release, and promotes brown fat over white.