HCAR - Hydroxy-Carboxylic Acid Receptor | Elisa - Clia - Antibody - Protein

Background:

The Hydroxy-Carboxylic Acid Receptors (HCARs) are a family of G protein-coupled receptors (GPCRs) that respond to hydroxy-carboxylic acids, such as lactate and β-hydroxybutyrate (BHB). These receptors play significant roles in metabolic regulation, energy homeostasis, and immune modulation. HCARs were identified as receptors for hydroxy-carboxylic acids in the early 2000s through pharmacological and molecular studies. HCARs respond to various hydroxy-carboxylic acids, including lactate, BHB, and other related metabolites. HCARs are expressed in various tissues, including adipose tissue, skeletal muscle, immune cells, and the central nervous system. HCAR1 is activated by lactate, a metabolite produced during glycolysis and lactate fermentation.It is also activated by BHB, a ketone body produced during fasting, low-carbohydrate diets, and ketogenic states.In summary, HCARs play crucial roles in metabolic regulation, immune modulation, and adipocyte function in response to hydroxy-carboxylic acids such as lactate and BHB.

Structural Features:

• G Protein-Coupled Receptors (GPCRs): HCARs belong to the GPCR superfamily, characterized by seven transmembrane domains.
• Topology: Like other GPCRs, HCARs consist of an extracellular N-terminus, seven transmembrane helices, and an intracellular C-terminus.

Subtypes and Classification:

1.   HCAR1: Also known as GPR81, primarily responds to lactate and is involved in metabolic regulation and adipocyte function.

2.   HCAR2: Also known as GPR109A, primarily responds to BHB and is involved in immune modulation and anti-inflammatory effects.

Physiological Functions:

• Metabolic Regulation: HCARs play roles in regulating energy metabolism, lipid metabolism, and glucose homeostasis.
• Immune Modulation: HCARs regulate immune cell function and inflammatory responses, contributing to the anti-inflammatory effects of BHB and lactate.
• Adipocyte Function: HCAR1 activation in adipocytes inhibits lipolysis and promotes fat storage, linking lactate metabolism to adipose tissue function.
• Neurological Effects: HCARs may also have neurological effects, although their roles in the central nervous system are less well understood.

Clinical Implications:

• Metabolic Disorders: Dysregulation of HCAR signaling has been implicated in metabolic disorders such as obesity, diabetes, and metabolic syndrome.
• Inflammatory Diseases: HCAR activation by BHB and lactate may have therapeutic potential in inflammatory diseases such as inflammatory bowel disease (IBD), psoriasis, and rheumatoid arthritis.
• Neurological Disorders: HCARs may be implicated in neurological disorders associated with altered energy metabolism and neuroinflammation.

Therapeutic Potential:

• Drug Development: HCAR agonists and antagonists are being investigated for their potential therapeutic applications in metabolic disorders, inflammatory diseases, and neurological conditions.
• Nutritional Interventions: Modulation of HCAR signaling through dietary interventions, such as ketogenic diets or supplementation with ketone bodies, may offer potential benefits for metabolic health and inflammatory conditions.