Difference between revisions of "Sambeat 2019 Nat Commun"
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|abstract=Supplementation with the NAD<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> levels and hinder diet-induced metabolic damage, highlighting the relevance of NRK1 as a therapeutic target for metabolic disorders. | |abstract=Supplementation with the NAD<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> levels and hinder diet-induced metabolic damage, highlighting the relevance of NRK1 as a therapeutic target for metabolic disorders. | ||
|editor=[[Plangger M]], | |editor=[[Plangger M]], | ||
|mipnetlab=CH Lausanne Canto C | |||
}} | }} | ||
{{Labeling | {{Labeling | ||
Latest revision as of 12:23, 30 September 2019
| 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. |
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 • O2k-Network Lab: CH Lausanne Canto C
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
