ArticleThe Journal of clinical investigation2009
beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.
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Who cites it
118 citing papers in PubMed, 232 citations in OpenAlex.
- Adipose Tissue Free Fatty Acid Storage In Vivo: Effects of Insulin Versus Niacin as a Control for Suppression of Lipolysis.Diabetes · 2015Trial
- Niacin and biosynthesis of PGD₂by platelet COX-1 in mice and humans.The Journal of clinical investigation · 2012 · on this mapTrial
- Effect of extended-release niacin on new-onset diabetes among hyperlipidemic patients treated with ezetimibe/simvastatin in a randomized controlled trial.Diabetes care · 2012Trial
- Article
- Therapeutic strategies for hypertension: exploring the role of microbiota-derived short-chain fatty acids in kidney physiology and development.Pediatric nephrology (Berlin, Germany) · 2026Review
- Article
- The predictive value of niacin skin flushing response and inflammatory factors for the antidepressant efficacy.BMC psychiatry · 2026Article
- Structural Perspectives on Biased Allostery of GPCR Signaling.Handbook of experimental pharmacology · 2026Review
- A Pathophysiologic Mechanism for the Treatment of Salt-Sensitive Hypertension and Heart Failure: The Role of β-Arrestins.Clinical drug investigation · 2026Review
- Hydroxycarboxylic acid receptor 2 (GPR109A) and retinopathies: pathways and prospects.Frontiers in medicine · 2026Review
- Niacin, an active form of vitamin B3, exerts antiviral function by recruiting β-arrestin through GPR109A to activate the phosphorylation of ERK and STAT1 axis.Journal of virology · 2025Article
- G Protein-Coupled Receptor Signaling: Implications and Therapeutic Development Advances in Cancers.MedComm · 2025Review
- Insights into the Activation Mechanism of HCA1, HCA2, and HCA3.Journal of medicinal chemistry · 2025Article
- β-Hydroxybutyrate enhances chondrocyte mitophagy and reduces cartilage degeneration in osteoarthritis via the HCAR2/AMPK/PINK1/Parkin pathway.Aging cell · 2024Article
- Multiple recent HCAR2 structures demonstrate a highly dynamic ligand binding and G protein activation mode.Nature communications · 2024Review
- Structure-guided engineering of biased-agonism in the human niacin receptor via single amino acid substitution.Nature communications · 2024Article
- Dietary niacin intake and mortality among chronic kidney disease patients.Frontiers in nutrition · 2024Article
- Structural insights into ligand recognition and selectivity of the human hydroxycarboxylic acid receptor HCAR2.Cell discovery · 2023Article
- Orthosteric and allosteric modulation of human HCAR2 signaling complex.Nature communications · 2023Article
- Structural basis for ligand recognition and signaling of hydroxy-carboxylic acid receptor 2.Nature communications · 2023Article
58 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Nicotinic acid is one of the most effective agents for both lowering triglycerides and raising HDL. However, the side effect of cutaneous flushing severely limits patient compliance. As nicotinic acid stimulates the GPCR GPR109A and Gi/Go proteins, here we dissected the roles of G proteins and the adaptor proteins, beta-arrestins, in nicotinic acid-induced signaling and physiological responses. In a human cell line-based signaling assay, nicotinic acid stimulation led to pertussis toxin-sensitive lowering of cAMP, recruitment of beta-arrestins to the cell membrane, an activating conformational change in beta-arrestin, and beta-arrestin-dependent signaling to ERK MAPK. In addition, we found that nicotinic acid promoted the binding of beta-arrestin1 to activated cytosolic phospholipase A2 as well as beta-arrestin1-dependent activation of cytosolic phospholipase A2 and release of arachidonate, the precursor of prostaglandin D2 and the vasodilator responsible for the flushing response. Moreover, beta-arrestin1-null mice displayed reduced cutaneous flushing in response to nicotinic acid, although the improvement in serum free fatty acid levels was similar to that observed in wild-type mice. These data suggest that the adverse side effect of cutaneous flushing is mediated by beta-arrestin1, but lowering of serum free fatty acid levels is not. Furthermore, G protein-biased ligands that activate GPR109A in a beta-arrestin-independent fashion may represent an improved therapeutic option for the treatment of dyslipidemia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.