Nicotinamide phosphoribosyltransferase

All right, Dr. Kuipers, where does chronobiology fit into this discussion on the metabolic side?

So circadian transcription factors like CLOCK and BMAL1 drive the expression of NAMPT, the rate-limiting enzyme in the NAD+ salvage pathway.

So when circadian rhythms are disrupted by late-night artificial light or shift work, NAMPT oscillations flattens.

Cellular NAD+ pools contract, and Sirt1 activity drops.

And these sirtuins, they require NAD+ to regulate histone deacetylation and DNA repair.

And toxic partners.

And once we've got rid of our toxic partners, kidding, we move to phase two, reestablish circadian and bioenergetic alignment.

So align circadian cues to restore NAMPT oscillations.

The first, we are joined by first author, Dr. Daniel Ferguson, who's an assistant professor, and then by corresponding author, Sandeep Mukherjee, who is an instructor of medicine, and both are in the Division of Nutritional Science and Obesity at WashU Medicine.

And they joined us to talk about their article on adipose tissue overexpression of nicotinamide phosphoribotransferase, or NAMPT, for those of you who know.

and how it prevents metabolic dysfunction in obese mice via extracellular vesicles.

We then chat with first author, sub-ismina root, and co-corresponding author, Dr. Ron He Chui from the Department of Nutrition and Integrative Physiology at the University of Utah Health about their article, Females are Completely Resistant to Semaglutide-Induced Muscle Loss in Obi-Obi Mice.

That's exactly correct.

So, although we saw those, like Sandeep was saying, we saw those dramatic effects between the male overexpressing mice and the non-expressing control mice, we found that females did not have the associated improvements in glucose tolerance or glucose metabolism.

However, when looking at the differences in NAMPT or NAMP expression by adipose tissue, we noticed that females had higher levels of NAMP relative to males and that in the adipose tissue, we could not see a significant increase in the overexpressing females versus the overexpressing control mice.

So with the help of John Tifo, they provided several samples for us.

Basically chronic low-grade inflammation drives CD38 up and accumulated DNA damage keeps PARPs busy.

And then NAMPT, which is the rate limiting recycling enzyme of NAD plus declines with aging inflammation.

So basically we have all these things that are chewing up more NAD plus over time.

And then basically, if you look at it, that practically, what does that mean for supplementation? Basically, as we get older, the only logical conclusion that a lot of us would draw is like, okay, well, if it's getting chewed up, we can either supplement with more of it or we can reduce inflammation, improve training, and sleep properly, or reduce the drain on NAD+.

One, we have the salvage pathway.

This is kind of the workhorse pathway that it's primarily done through.

It recycles nicotinamide waste back into NAD+, and then NAMPT is the bottleneck.

Most of the NAD+, and the body comes from this loop.