NREndogenous nicotinamide riboside metabolism protects against diet-induced liver damage

Fred
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Joined: Tue Aug 13, 2019 3:17 pm
Location: Stockholm, Sweden

Endogenous nicotinamide riboside metabolism protects against diet-induced liver damage

Post by Fred » Fri Sep 20, 2019 3:21 pm

More proof that NAD precursors do more than the vitamin nicotinamide (NAM). NMN is NR with a phosphate-group attached to it, so they should behave similarly but that is unknown until tested.

"NR drives NAD+ biosynthesis through a highly conserved path from yeast to mammals. It is initiated with the phosphorylation of NR by NR Kinases (NRK1 or NRK2), generating NMN which is subsequently converted in NAD+ via NMN adenylyl transferase enzymes (NMNATs)"

Supplementation with an alternative NAD+ precursor (nicotinamide) did not prevent the defects of the NRK1 deficient mice and failed to restore NAD+. NRK1 is essential and rate-limiting for NAD+ synthesis from exogenous NR and NMN in hepatocytes.

This shows that in mice NAD+ precursors are not fully exchangeable and NR, compared to nicotinamide, has a unique ability to sustain high hepatic NAD-levels and this is important for DNA-repair.

Endogenous nicotinamide riboside metabolism protects against diet-induced liver damage

Published in NATURE: 20 September 2019
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.
https://www.nature.com/articles/s41467-019-12262-x


Fred
Registered dietitian, Sweden.
Drdavid
Posts: 209
Joined: Thu Aug 15, 2019 9:59 am

Re: Endogenous nicotinamide riboside metabolism protects against diet-induced liver damage

Post by Drdavid » Sun Sep 22, 2019 8:53 pm

Thanks Fred this is a great article. A group of ER physicians were talking about hepatic damage after overdose of Tylenol. I had brought up that NAD should be considered as a possible complimentary treatment. This article will be good source.
Fred
Posts: 127
Joined: Tue Aug 13, 2019 3:17 pm
Location: Stockholm, Sweden

Re: Endogenous nicotinamide riboside metabolism protects against diet-induced liver damage

Post by Fred » Mon Sep 23, 2019 3:45 am

Good thinking. NAC for the ROS-damage and NAD+ precursors to aid in bioenergetics for the hepatocytes to handle DNA-repair.
Fred
Registered dietitian, Sweden.
Drdavid
Posts: 209
Joined: Thu Aug 15, 2019 9:59 am

Re: Endogenous nicotinamide riboside metabolism protects against diet-induced liver damage

Post by Drdavid » Mon Sep 23, 2019 10:16 pm

I had seen in Germany that the NAC/NAD protocol was being used with great results. It makes sense.
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