Deletion of single enzyme stops mice getting fat, no matter the diet
A compelling study from a team of researchers at the University of Copenhagen has demonstrated a way to completely stop a body's ability to store fat. In experiments with mice, the team showed that genetically deleting a single enzyme resulted in the animal not being able to gain weight, even when fed a fatty diet.
An enzyme dubbed NAMPT has been connected to obesity in both human and animal models by several studies. Its presence in fat tissue has been found to increase metabolic functionality in numerous body tissues, including fat tissue, which enhances the body's ability to store fat.
"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," says Zachary Gerhart-Hines, a corresponding author on the study.
In order to understand the effects of this vital enzyme the researchers engineered mice lacking NAMPT in fat tissue. When the engineered mice were subsequently fed a high-fat diet they were unable to gain weight. Compared to a control group on the same diet that became obese, the NAMPT-lacking mice also seemed to be able to better control their blood glucose levels despite the unhealthy fatty diet.
'We gave the mice a diet that more or less corresponds to continuously eating burgers and pizza," explains Karen Nørgaard Nielsen, first author on the study. "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 metabolic disease."
The study is undeniably fascinating but unfortunately the researchers suggest it cannot be directly transferred into a therapy for humans. NAMPT is an enzyme found to be expressed across a variety of organs and tissues, so directly inhibiting it in humans could result in many harmful off-target side-effects.
Interestingly, NAMPT inhibitors are also being investigated for cancer therapies, with recent research demonstrating synthesized molecules can be developed that specifically target tumors resulting in cell death.
Further research is proposed to investigate exactly how a deficiency in NAMPT inhibits fat storage and obesity. It is hoped that understanding the mechanism at play could help researchers develop a more targeted treatment strategy that regulates fat storage without causing the broader systemic issues that would result from entirely eliminating NAMPT from a body.
The research was published in the journal Molecular Metabolism.
Source: University of Copenhagen