NMN supplementation promotes liver growth-The result of the regulated transcription and metabolism

Abstract

Abstract Immunodeficient individuals are not only prone to infections, endangering the health, but also encounter restricted growth and development. In the present study, we confirmed the role of NMN and found the preferred supplementation dosage in promoting liver growth of immunodeficient mice in vivio, and explored the underlying mechanism. Fifty 8-week-old inbred BALB/c immunodeficient mice were randomly divided into placebo Control group (C), Low-dosage NMN supplementation group (N50), Medium-dosage NMN supplementation group (N100), High-dosage supplementation NMN group (N200) and NMN + 78c supplementation group (N100 + 78c), with 10 mice in each group. In the low, medium and high NMN supplementation groups, mice were supplemented with 50 mg/kg/d, 100 mg/kg/d and 200 mg/kg/d NMN by gavage respectively for 21 days. During the period of supplementation with 100 mg/kg/d, 78c was supplemented to the mice by intraperitoneal injection on the first, eighth and 15th day of the 21 days. On the next day after supplementation treatment, the mice were anesthetized and the livers were excised and weighted. The expression of GHR, IGF-1, SIRT1, YAP1, p-YAP1, JAK1 and STAT3 was detected by Western Blot, the co-localisation level of SIRT1-JAK1, SIRT1-STAT3, JAK1-STAT3, YAP1-JAK1 and YAP1-STAT3 were detected by the immunofluorescence double labeling technique. Untargeted metabolomics was detected for analysing the effects of NMN on liver metabolism. It was found that the weight of the liver of mice in N100 group increased compared with C group, and the expression of SIRT1, JAK1, STAT3, YAP1, GHR and IGF-1 was increased. The co-localisation level of SIRT1-JAK1, JAK1-STAT3, YAP1-JAK1 and YAP1-STAT3 was increased after the supplementation of 100 mg/kg/d NMN. These changes were not significant in N50 and N200 groups. Upon the injection of 78c, the effect of NMN on transcription was inhibited, suggesting that the effect was CD38 dependent. We also found that, the improved amino acid metabolism after NMN supplementation was supposed to be one of the important mechanisms underlying liver growth.