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June 2014


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The beta-hydroxybutyrate receptor HCA2 activates a neuroprotective subset of macrophages, Nature Communications (2014), doi:10.1038/ncomms4944 (DZHK authors: Müller-Fielitz, Offermanns, Schwaninger)

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Ketone bodies serve as a source of energy for the heart muscle and brain. They also have a protective effect in ischemic stroke. But whether the protective effect of the ketone bodies is due to their supply of energy was unclear. By binding to the G-protein coupled HCA2 receptor in lipocytes and immunocytes, the ketone body beta-hydroxybutyrate also serves regulatory functions. In order to clarify the function of HCA2 in stroke, DZHK investigators led by Markus Schwaninger (Lübeck) examined the effect of a ketogenic diet in mice that lacked HCA2. They found that HCA2 mediates the effect of a ketogenic diet. Further analyses showed that monocytes and macrophages that are derived from the bone marrow and migrate to the brain are responsible for the effect of HCA2. HCA2 appears to activate protective properties in these cells. Fortunately, various HCA2 agonists already exist which can now be tested in models of ischemia. The researchers report on their findings in Nature Communications doi:10.1038/ncomms4944.