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Regular nicotinic acid ("niacin") as effective as NR in raising NAD+ levels in mice hepatocytes (cell culture)

nicotinic acid tryptophan hepatocytes nampt liver mitochondrial function

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#1 Fredrik

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Posted 12 August 2019 - 07:57 AM


Role of NAMPT for maintaining liver mitochondrial function
 

CELL CULTURE

 

"Stimulation with different NAD + precursors showed differential effects on hepatocyte NAD + levels.

 

NR and NMN induced a rapid increase in cellular NAD + levels. The ability of NR to increase cellular NAD + levels has been demonstrated across multiple cell lines (12) and in primary mouse hepatocytes (29).

 

NA and Trp were not efficient precursors for NAD + after 6 hours, but prevented a decline in NAD + content in HNKO mice after 24 and 48 hours of incubation.

 

NA and Trp may not be capable of increasing NAD + levels after 6 hours due to the culturing media used, as this media contains 50 µM Trp and 200 nM of NAM and NA, respectively.

 

The presence of these metabolites may mask true precursor utilization capacities in the stimulated wells.

 

When cells were stimulated with NA and tryptophan for 6 hours following 48 hours of NAD + depletion and without replacing the media, NA was as potent as NR, and caused a much higher increase in NAD + content than Trp. Moreover, we found that tryptophan contributes to the maintenance of the NAD + pool, but that it is not efficient at increasing total NAD + content. This is in line with a recent report, demonstrating that primary hepatocytes can utilize Trp to generate NAD + , but to a much lower degree than full liver."

 

 

IN VIVO, whole liver

 

"NR was stable in the drinking water, and oral NR administration significantly increased hepatic NAD+ and NADP + levels. However, NR did not prevent fat mass accumulation or improve glucose tolerance as previously reported (7, 12), but decreased plasma HDL and LDL/VLDL levels as

reported earlier (12). However, dietary NR supplementation for 12 weeks in obese, older, and dyslipidemic men was recently shown to not affect plasma levels of LDL, HDL, or total cholesterol (32). Intriguingly, our data revealed that while NR increased oxygen consumption following induction of State III respiration in WT mice, this was not observed in HNKO mice. No genotype effects were observed following FCCP stimulation, demonstrating that maximal uncoupled respiratory capacity was not compromised in the HNKO liver. At present, we have no explanation for this observation, but since NR increased NAD + levels in both genotypes, the underlying cause may be unrelated to reduced NAD + content induced by knockout of Nampt.
 
In conclusion, NAMPT plays an important role to maintain NAD + levels in hepatocytes. However, lack of NAMPT has only minor effects on mitochondrial function measured either in vitro or ex vivo. While NR was able to increase hepatic NAD + levels in both cell cultures and whole liver, and showed positive effects on the blood lipid profile in response to HFD feeding, it did not significantly affect hepatic triglyceride content, glucose tolerance, or whole-body fat mass accumulation in HFD-fed mice. Future studies will be directed towards clarifying the contribution of individual hepatic NAD + salvage pathways as well as the de novo synthesis pathway in response to dietary interventions that exert a more profound metabolic stress on the liver."
 

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Also tagged with one or more of these keywords: nicotinic acid, tryptophan, hepatocytes, nampt, liver mitochondrial function

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