Niacin receptor 1

Niacin receptor 1, also known as NIACR1 or GPR109A, is a is_associated_with::protein which in humans is encoded by the NIACR1 is_associated_with::gene.

Function
NIACR1 is a high-affinity Gi/Go-coupled is_associated_with::G protein-coupled receptor (GPCR) for is_associated_with::nicotinic acid (niacin), and is a member of the nicotinic acid receptor family of GPCRs (the other identified member being is_associated_with::Niacin receptor 2, also known as is_associated_with::GPR109B). Butyrate is also another common ligand (is_associated_with::full agonist) of NIACR1.  Figure 1: Microbial-derived molecules promote colonic Treg differentiation.

Clinical significance
Niacin receptor 1 is an important biomolecular target of niacin which is a widely prescribed drug for the treatment of is_associated_with::dyslipidemia and to increase HDL cholesterol but whose therapeutic use is limited by flushing. In NIACR1 knockout mice, the effects of niacin on both lipids and flushing is eliminated. Furthermore, in is_associated_with::arrestin beta 1 knockout mice, niacin's effect on flushing is greatly reduced while the lipid modifying effects are maintained.

The precise mechanism of action of niacin therapeutic effects has not been fully elucidated, but appears to work in part through activation of NIACR1 which reduces the levels of intracellular cAMP thereby inhibiting is_associated_with::lipolysis in is_associated_with::adipocytes. In contrast, the flushing effect is due to NIACR1 activation of ERK 1/2 MAP kinase mediated by is_associated_with::arrestin beta 1. Activation of MAP kinase in turn causes release of is_associated_with::prostaglandin D2 from is_associated_with::Langerhans cells in the skin.

5-oxo-ETE
The mouse ortholog of NIACR1, Niacr1, has recently been proposed to mediate the ability of 5-oxo-ETE, a member of the is_associated_with::5-HETE family of eicosanoids, to stimulate the production of is_associated_with::steroidogenic acute regulatory protein mRNA, Steroidogenic acute regulatory protein, and thereby progesterone in mouse cultured MA-10 is_associated_with::Leydig cells. Human tissues respond to 5-oxo-ETE and other 5-HETE family members though the is_associated_with::OXER1 G protein-coupled receptor. The roles, if any, of Niacr1 in the response of leydig cells to other 5-HETE family members, of Niacr1 in the response of other mouse cells to 5-HETE family members, and the role of NIACR1 in the response of human tissues to 5-HETE family members has not been determined.