Sambeat 2019 Nat Commun

Sambeat A, Ratajczak J, Joffraud M, Sanchez-Garcia JL, Giner MP, Valsesia A, Giroud-Gerbetant J, Valera-Alberni M, Cercillieux A, Boutant M, Kulkarni SS, Moco S, Canto C (2019) Endogenous nicotinamide riboside metabolism protects against diet-induced liver damage. Nat Commun 10:4291.

» PMID: 31541116 Open Access

Sambeat A, Ratajczak J, Joffraud M, Sanchez-Garcia JL, Giner MP, Valsesia A, Giroud-Gerbetant J, Valera-Alberni M, Cercillieux A, Boutant M, Kulkarni SS, Moco S, Canto C (2019) Nat Commun

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.

• Bioblast editor: Plangger M

Labels: MiParea: Respiration, Genetic knockout;overexpression 

Organism: Mouse  Tissue;cell: Skeletal muscle, Liver  Preparation: Permeabilized tissue, Homogenate 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, NS  HRR: Oxygraph-2k 

Labels, 2019-09