2. Signaling Pathways
  3. GPCR/G Protein
  4. Hydroxycarboxylic Acid Receptor (HCAR)
  5. HCAR2 Isoform

HCAR2

GPR109A; Niacr1

HCAR2 (hydroxycarboxylic acid receptor 2, also known as GPR109A) is a G protein-coupled receptor (GPCR) that functions as a metabolic and immune sensor linking nutrient-derived metabolites to cellular signaling pathways[1][1]. Activation of HCAR2 by endogenous ligands such as β-hydroxybutyrate and by pharmacological agonists including niacin initiates Gi-dependent signaling, suppresses inflammatory responses, and regulates lipid metabolism[1][2]. Mechanistically, HCAR2 signaling reduces pro-inflammatory cytokine production, modulates macrophage activation, and attenuates microglial reactivity, thereby contributing to immune homeostasis and neuroinflammatory control[1][3][4]. In disease models, HCAR2 activation has been associated with protection against colonic inflammation, colorectal tumorigenesis, atherosclerosis, and neuroinflammatory disorders, supporting its value as a therapeutic and experimental target in inflammation-related research[3][4][5]. Compared with related hydroxycarboxylic acid receptor family members, HCAR2 and HCAR3 share exceptionally high sequence similarity, yet differ in ligand recognition and binding-pocket architecture, resulting in distinct pharmacological profiles and receptor selectivity[2][6]. Structural studies further demonstrated that niacin and acipimox preferentially activate HCAR2, whereas subtype-selective agonists such as MK-6892 exhibit markedly greater specificity for HCAR2 than for HCAR3[6]. Therefore, selective HCAR2 agonists provide useful tools for dissecting receptor-specific signaling mechanisms and evaluating anti-inflammatory pathways in preclinical disease models[1][6].

HCAR2 Related Products (1):

Cat. No. Product Name Effect Purity
  • HY-30216A
    Leucic acid
    		98.38%
    Leucic acid (α-Hydroxyisocaproic acid) is an orally active end-product of the microbial metabolism of leucine. Leucic acid can bind to HCAR2, alters AMPK and ERK1/2 phosphorylation status, suppresses lipid synthesis, promotes catabolism, reduces adiposity, enhances lean mass and exercise capacity. Leucic acid suppresses pro-inflammatory cytokine secretion, inflammation-related gene mRNA expression. Leucic acid decreases basal protein synthesis, attenuates myotube atrophy. Leucic acid can be used for the research of obesity.