Nat Neurosci: Zhang Guo/Cai Dongsheng/Li Juxue Team Finds That Inhibiting Tak1 Reverses Obesity-Related Cerebrovascular Disorder

Long-term obesity is associated with cerebrovascular dysfunction, however, our basic mechanisms are still unclearin a recent study using a long-term obese mouse model with basal artery (BA) abnormalities, researchers found that the small glial conversion growth factor beta-activated kinase 1 (Tak1) was overactive in the brain stemdrug suppression of Tak1 in brain stem or selective removal of Tak1 in small glial cells improved BA vascular dysfunctionConversely, in normally fed mice, specific activation of Tak1 in small glial cells in the brain stem was sufficient to cause BA dysfunctionMechanism, Tak1 activation leads to an increase in the production of leukocyte interleukin-18 (IL-18), while in the context of long-term obesity, blocking IL-18 receptors in the brain helps protect the cerebrovascular dysfunctionThe selective removal of Tak1 by small glial cells also protects individuals from chronically obese brain ischemic strokesin summary, these findings provide evidence that Tak1, a small glial cell in the brain, especially in the brain stem, is involved in the pathogenesis of obesity-related cerebrovascular dysfunction