| First Author | Sambeat A | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 4291 |
| PubMed ID | 31541116 | Mgi Jnum | J:279424 |
| Mgi Id | MGI:6362426 | Doi | 10.1038/s41467-019-12262-x |
| Citation | Sambeat A, et al. (2019) Endogenous nicotinamide riboside metabolism protects against diet-induced liver damage. Nat Commun 10(1):4291 |
| abstractText | Supplementation with the NAD(+) precursor nicotinamide riboside (NR) ameliorates and prevents a broad array of metabolic and aging disorders in mice. However, little is known about the physiological role of endogenous NR metabolism. We have previously shown that NR kinase 1 (NRK1) is rate-limiting and essential for NR-induced NAD(+) synthesis in hepatic cells. To understand the relevance of hepatic NR metabolism, we generated whole body and liver-specific NRK1 knockout mice. Here, we show that NRK1 deficiency leads to decreased gluconeogenic potential and impaired mitochondrial function. Upon high-fat feeding, NRK1 deficient mice develop glucose intolerance, insulin resistance and hepatosteatosis. Furthermore, they are more susceptible to diet-induced liver DNA damage, due to compromised PARP1 activity. Our results demonstrate that endogenous NR metabolism is critical to sustain hepatic NAD(+) levels and hinder diet-induced metabolic damage, highlighting the relevance of NRK1 as a therapeutic target for metabolic disorders. |
