Patients with narcolepsy have higher body mass indices (BMIs) comparing the general population. In contrast, diabetes model mice have decreased numbers of orexin neurons in the lateral hypothalamic area. Importantly, the prolonged exposure of Figure 1. Epigenetic status before and after establishing hiONs from hiPSCs and epigenetic silencing by hyperglycemia in orexin neurons(A) Epigenetic status in HCRT expressing and non-expressing cells on HCRT gene locus. (B) Hexosamine biosynthetic pathway (HBP) and sialic acid synthetic pathway. Some glucose is metabolized by the HBP into UDP-Figure 2. Activities ManNAc derivatives for HCRT gene expression in neural cells derived from hiPSCs The activities of ManNAc, ManNFAc, 5S-ManNAc, 5S-ManNAcF, ManNCOOMe, and ManNCOOEt were evaluated by the expression of HCRT expression normalized to ACBT levels.biosynthetic pathway, generating the fluorine substituted GM3-BODIPY, 5S-ManNAc, another potent derivative, was not incorporated into the glycolipid, suggesting that the observed actions of ManNAc derivatives are sialic acid independent.GlcNAc, ManNAc, and sialic acid. UDP-GlcNAc is used to modify O-GlcNAc in cells, while sialic acid is essential for extra-cellular bioactivity. ManNAc is an intermediate of UDP-GlcNAc and is a precursor of sialic acid. 51
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