ArticleFrontiers in endocrinology2011
Biological roles and therapeutic potential of hydroxy-carboxylic Acid receptors.
Article in Frontiers in endocrinology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 62 citations in OpenAlex.
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- Stachyose attenuates DSS-induced colitis and is associated with elevated colonic medium-chain fatty acids: an integrated multi-omics analysis.NPJ science of food · 2025Article
- The Therapeutic Effect of GPR81 in Autoimmune Hepatitis and Hepatocellular Carcinoma via Regulating the Immune Response.International journal of molecular sciences · 2025Article
- Insights into the Activation Mechanism of HCA1, HCA2, and HCA3.Journal of medicinal chemistry · 2025Article
- Network Pharmacology and Serum Nontargeted Metabolomics Reveal the Protective Effects of Propionate Against Liver Damage Induced by a High-Fat and AGE-Rich Diet in Diabetic Mice.Journal of diabetes research · 2025Article
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- Exploring Microbial Metabolite Receptors in Inflammatory Bowel Disease: An In Silico Analysis of Their Potential Role in Inflammation and Fibrosis.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Metformin increases 3-hydroxy medium chain fatty acids in patients with type 2 diabetes: a cross-sectional pharmacometabolomic study.Frontiers in endocrinology · 2024Article
- Lactate: an alternative pathway for the immunosuppressive properties of mesenchymal stem/stromal cells.Stem cell research & therapy · 2023Article
- The lipolysis inhibitor acipimox reverses the cardiac phenotype induced by electronic cigarettes.Scientific reports · 2023Article
- The Promise of Niacin in Neurology.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- Cancer Metabolism: Fasting Reset, the Keto-Paradox and Drugs for Undoing.Journal of clinical medicine · 2023Review
- Understanding the Contribution of Lactate Metabolism in Cancer Progress: A Perspective from Isomers.Cancers · 2022Review
- Neuronal GPR81 regulates developmental brain angiogenesis and promotes brain recovery after a hypoxic ischemic insult.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- Repurposing Dimethyl Fumarate for Cardiovascular Diseases: Pharmacological Effects, Molecular Mechanisms, and Therapeutic Promise.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Lactate drives cellular DNA repair capacity: Role of lactate and related short-chain fatty acids in cervical cancer chemoresistance and viral infection.Frontiers in cell and developmental biology · 2022Review
- Rare and potentially pathogenic variants in hydroxycarboxylic acid receptor genes identified in breast cancer cases.BMC medical genomics · 2021Article
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the recent past, deorphanization studies have described intermediates of energy metabolism to activate G protein-coupled receptors and to thereby regulate metabolic functions. GPR81, GPR109A, and GPR109B, formerly known as the nicotinic acid receptor family, are encoded by clustered genes and share a high degree of sequence homology. Recently, hydroxy-carboxylic acids were identified as endogenous ligands of GPR81, GPR109A, and GPR109B, and therefore these receptors have been placed into a novel receptor family of hydroxy-carboxylic acid (HCA) receptors. The HCA(1) receptor (GPR81) is activated by the glycolytic metabolite 2-hydroxy-propionic acid (lactate), the HCA(2) receptor is activated by the ketone body 3-hydroxy-butyric acid, and the HCA(3) receptor (GPR109B) is a receptor for the β-oxidation intermediate 3-hydroxy-octanoic acid. While HCA(1) and HCA(2) receptors are present in most mammalian species, the HCA(3) receptor is exclusively found in humans and higher primates. HCA receptors are expressed in adipose tissue and mediate anti-lipolytic effects in adipocytes through G(i)-type G protein-dependent inhibition of adenylyl cyclase. HCA(2) and HCA(3) inhibit lipolysis during conditions of increased β-oxidation such as prolonged fasting, whereas HCA(1) mediates the anti-lipolytic effects of insulin in the fed state. As HCA(2) is a receptor for the established anti-dyslipidemic drug nicotinic acid, HCA(1) and HCA(3) also represent promising drug targets and several synthetic ligands for HCA receptors have been developed. In this article, we will summarize the deorphanization and pharmacological characterization of HCA receptors. Moreover, we will discuss recent progress in elucidating the physiological and pathophysiological role to further evaluate the therapeutic potential of the HCA receptor family for the treatment of metabolic disease.
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