Deletion of single enzyme stops mice getting fat, no matter the diet

At the University of Copenhagen, a study from a team of researchers has demonstrated a way to completely stop a body’s ability to store fat. In experiments with mice, with this experiment, the team showed up that deleting one enzyme resulted in the animal to not being able to gain weight, even if the animal is fed fatty diet.

An enzyme dubbed NAMPT has now been connected with obesity in both the human as well as animal models by several studies. This enzyme’s presence in fat tissues has been found for increasing metabolic functionality of numerous body tissues; including the fat tissues that help in enhancing the ability of a body to store fat.

Zachary Gerhart-Hines, a corresponding author on the study, stated that- “NAMPT in fat tissue was likely once an extraordinary benefit to our ancestors but in today’s society full of high-fat, calorically-dense foods, it may now pose a liability”.

For understanding the effects of this vital enzyme the researchers worked on mice lacking NAMPT in fat tissue. When these engineered mice were fed a diet of high fat they were unable to gain weight. In comparison to a control group with the same diet that became overweight, the NAMPT-lacking mice were also observed to be able to better control their blood glucose levels regardless of the unhealthy fatty diet.

Here, the high-fat-diet mice were fed a lard-like substance with 45 percent of its calories from fat. Control mice were fed standard chow with 4.5 percent of its calories from fat. The dietary regimen began when the mice were 8 weeks old and continued for 14 to 16 weeks.

Karen Nørgaard Nielsen, the first author on the study explained that- ‘We gave the mice a diet that more or less corresponds to continuously eating burgers and pizza’. “Still, it was impossible for them to expand their fat tissue. Our ultimate goal is that by understanding these fundamental underpinnings of how we become obese, we can apply our finding to the development of novel treatment strategies for the metabolic disease.”

The study has been undeniably fascinating but unfortunately, the researchers suggest that it cannot be directly transferred into a therapy for humans. NAMPT is an enzyme that is found to be expressed as a variety of organs and tissues. So, if we try directly inhibiting it in humans this could possibly result in many harmful off-target side-effects.

The NAMPT inhibitors are also being investigated for some of the cancer therapies, furthermore with recent researches demonstrating the synthesized molecules can be developed that specifically target tumors in cell death. Some later researches were proposed for investigating exactly how a deficiency in NAMPT inhibits fat storage and obesity.

It is also hoped that understanding the mechanism at play could help researchers in developing a more targeted treatment strategy that will later help to regulate fat storage without causing the broader systemic issues that would result in entirely eliminating NAMPT from a body.

This research was funded by the National Institutes of Health and the American Diabetes Association. All animal use was conducted in compliance with the Institute of Laboratory Animal Research’s Guide for the Care and Use of Laboratory Animals and was approved by the University Committee on Use and Care of Animals at the University of Michigan.

The research was later published in the journal Molecular Metabolism.

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