Hydroxy-carboxylic acid receptors (HCA1-3) are a family of G-protein-coupled receptors that regulate lipolysis. HCAR2 (GPR109A) was identified as the receptor for nicotinic acid (niacin; vitamin B3) and beta-hyroxybutyrate (β-OHB), a ketone body synthesized by the liver under negative energy balance¹.

HCAR2 is mainly expressed on adipocytes and immune cells and in lower levels in retinal pigmented and colonic epithelial cells, microglia and normal mammary tissue. High levels of HCAR2 can be found in immune cells such as macrophages in response to the presence of interferon-γ, TNF-α and hypoxia².

HCAR2 activity in adipocytes promotes inhibition of adenylate cyclase and decrease cAMP levels. HCAR2 activity leads to a rapid decrease in lipolysis and reduction in the release of fatty acids from the adipocytes³.

Activation of HCAR2 has also been associated with anti-inflammatory effects in different disease states such as sepsis, diabetes and obesity. Interaction of HCAR2 with niacin and β-OHB under this conditions lead to variety of signaling events involving inflammatory downstream targets⁴.