| First Author | Rahman M | Year | 2014 |
| Journal | Nat Commun | Volume | 5 |
| Pages | 3944 | PubMed ID | 24845831 |
| Mgi Jnum | J:274128 | Mgi Id | MGI:6296232 |
| Doi | 10.1038/ncomms4944 | Citation | Rahman M, et al. (2014) The beta-hydroxybutyrate receptor HCA2 activates a neuroprotective subset of macrophages. Nat Commun 5:3944 |
| abstractText | The ketone body beta-hydroxybutyrate (BHB) is an endogenous factor protecting against stroke and neurodegenerative diseases, but its mode of action is unclear. Here we show in a stroke model that the hydroxy-carboxylic acid receptor 2 (HCA2, GPR109A) is required for the neuroprotective effect of BHB and a ketogenic diet, as this effect is lost in Hca2(-/-) mice. We further demonstrate that nicotinic acid, a clinically used HCA2 agonist, reduces infarct size via a HCA2-mediated mechanism, and that noninflammatory Ly-6C(Lo) monocytes and/or macrophages infiltrating the ischemic brain also express HCA2. Using cell ablation and chimeric mice, we demonstrate that HCA2 on monocytes and/or macrophages is required for the protective effect of nicotinic acid. The activation of HCA2 induces a neuroprotective phenotype of monocytes and/or macrophages that depends on PGD2 production by COX1 and the haematopoietic PGD2 synthase. Our data suggest that HCA2 activation by dietary or pharmacological means instructs Ly-6C(Lo) monocytes and/or macrophages to deliver a neuroprotective signal to the brain. |
