Format

Send to

Choose Destination
Nat Commun. 2019 Sep 20;10(1):4291. doi: 10.1038/s41467-019-12262-x.

Endogenous nicotinamide riboside metabolism protects against diet-induced liver damage.

Author information

1
Nestlé Research, EPFL Innovation Park, 1015, Lausanne, Switzerland.
2
School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015, Lausanne, Switzerland.
3
Nestlé Research, EPFL Innovation Park, 1015, Lausanne, Switzerland. carlos.cantoalvarez@rd.nestle.com.
4
School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015, Lausanne, Switzerland. carlos.cantoalvarez@rd.nestle.com.

Abstract

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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center