Using genetic engineering technology, scientists have found a way to make mice “completely resistant” to becoming obese, even when given a high-fat diet. The researchers say their discovery could open up new possibilities for the treatment of obesity in humans.
In a recent study published in Molecular Metabolism, researchers at the University of Copenhagen deleted an enzyme called NAMPT in the fat tissue of mice. Doing so appeared to “completely block” the mice from developing obesity.
The human body is highly efficient when it comes to storing fat from food sources. Although beneficial for our ancestors during times of food scarcity, this evolutionary trait has become problematic in modern times, researchers say.
“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,” study author Zachary Gerhart-Hines, an associate professor at the University of Copenhagen, said in a press release published on Thursday.
After deleting the NAMPT enzyme from fat tissue in some of the mice, researchers fed one group a healthy diet and another group “a diet that more or less corresponds to continuously eating burgers and pizza” for humans, said Karen Nørgaard Nielsen, lead author and Ph.D. student at the Novo Nordisk Foundation Centre for Basic Metabolic Research. The team then monitored the responses in the mice’s bodies.
When given a healthy, low-fat diet, there was no difference in body weight or amount of fat tissue for mice with and without the NAMPT enzyme. When given a high-fat diet, however, the control group of mice became obese, while the mice lacking the NAMPT enzyme did not. “It was impossible for them to expand their fat tissue,” explained Nørgaard Nielsen.
The findings are consistent with results of studies regarding NAMPT in humans, which have shown that being overweight or obese is linked to high amounts of the enzyme in blood and stomach fat tissue. Researchers said their study is the first to show that the NAMPT enzyme is necessary for the development of obesity and that an absence of the enzyme blocks obesity from occurring.
However, Gerhart-Hines cautioned that decreasing NAMPT in the human body is not a feasible treatment strategy for obesity, since the risk of harmful consequences in other tissues would be too high.
“NAMPT appears to increase the metabolic functionality of almost every tissue in the body in which it has been studied. For example, there are indications that the liver and skeletal muscle may benefit from increased NAMPT activity,” he said.
Instead, the authors hope their findings will lay the groundwork for future research into the links between NAMPT and fat storage, with the aim of one day finding new treatments for obesity and metabolic disorders.
“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,” said Nørgaard Nielsen.