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Role of NAMPT in liver gene expression in diabetic mice

ABSTRACT: We tested they hypothesis that hepatocyte NAMPT mediates transcriptomic changes in diabetic mice

ORGANISM(S): Mus musculus

PROVIDER: GSE184513 | GEO | 2021/09/21

REPOSITORIES: GEO

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Role of SIRT1 in NAMPT-induced liver gene expression

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Role of NAMPT in liver gene expression in diabetic mice

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The role of nicotinamide phosphoribosyltransferase (Nampt) in hippocampal neural stem/progenitor cells

Project description:Neural stem/progenitor cell (NSPC) proliferation and self-renewal, as well as insult-induced differentiation, decrease markedly with age, but the molecular mechanisms responsible for these declines remain unclear. Here we show that levels of NAD+ and nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme in mammalian NAD+ biosynthesis, decrease with age in the hippocampus. Ablation of Nampt in adult NSPCs reduced their pool and proliferation in vivo. The decrease in the NSPC pool during aging can be rescued by enhancing hippocampal NAD+ levels. Nampt is the main source of NSPC NAD+ levels and required for G1/S progression of the NSPC cell cycle. Nampt is also critical for oligodendrocytic lineage fate decisions through a mechanism mediated redundantly by Sirt1 and Sirt2. Ablation of Nampt in the adult NSPCs in vivo reduced NSPC-mediated oligodendrogenesis upon injury. These phenotypes recapitulate defects in NSPCs during aging, implicating Nampt-mediated NAD+ biosynthesis as a mediator of these age-associated functional declines. Total RNA obtained from neurospheres derived from postnatal hippocampi subjected to 48 hours in vitro of incubation with Nampt-specific inhibitor FK866 (10 nM, 4 samples) or vehicle (DMSO, 1:1000, 4 samples).

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Screening of genes differentiating transcriptional profiles of CIA rats at different NAMPT expression statuses

Project description:We screened out differentially expressed genes between CIA rats and healthy controls at both NAMPT++ (CIA1) and NAMPT+ (CIA2) statuses.It was obvious that that high expression of NAMPT is linked to acute inflammation, as TLRs and its downstream MAPKs and NF-κB were identified as the most affected pathways in NAMPT++ samples compared with normal control. However, by the decrease of NAMPT expression, the pathological situation was not eased but became even more complicated. Energy metabolism (mainly lipid metabolism) was significantly altered at this status. Interestingly, many RA-related pathways emerged, such as TGF-β, IL-17, PI3K-AKT and osteoclast differentiation pathways. These results solidly support the hypothesis that NAMPT overexpression is an early event in CIA and directly affects the innate rather than adaptive immunity.

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RNAi profiling of human MCF-7 cells depleted for NAMPT knockdown

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