Researchers defy biology

Mice remain slim on burger diet

University of Copenhagen The Faculty of Health and Medical Sciences

We are our own worst enemy when it comes to developing obesity. 

The body is naturally geared to assimilate energy from the food we eat and store it as fat until it is needed. 

This is the result of millions of years of evolution under the pressure of low food availability.

But today, where many of us have constant access to high calorie foods, our body's impressive ability to convert food into fat has, ironically, become problematic. 

Consequently, the number of overweight people worldwide is skyrocketing, leading to large health consequences for both the individual and society.

However, as part of a new study, researchers at the University of Copenhagen have now managed to inhibit the body's ability to store fat. They genetically delete the enzyme NAMPT in fat tissue of mice, and this renders the animals completely resistant to becoming overweight or obese, even on a very fatty diet.

'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 metabolic disease,' says Karen Nørgaard Nielsen, first author on the publication and a Ph.D. student at the Novo Nordisk Foundation Center for Basic Metabolic Research.

High-Fat Food, Same Weight

The findings are in line with results obtained from humans. Several studies have shown that the presence of large amounts of the enzyme NAMPT in blood and in stomach fat tissue is significantly connected with being overweight or obese. However, this study provides the first evidence that NAMPT is absolutely required to become overweight or obese and that lack of NAMPT in fat tissue fully protects against obesity.

In the University of Copenhagen study, the researchers compared how normal mice and mice lacking NAMPT in fat tissue gained weight when given either high-fat food or a healthier, lower-fat diet. When on the healthy diet, there was no difference in body weight or the amount of fat between the normal mice and the mice lacking NAMPT.

However, when the mice were given high-fat food, the control mice became very obese, yet the mice lacking NAMPT gained no more weight from high-fat food than when they were on the healthier diet. In addition, the mice lacking NAMPT maintained better control of blood glucose than normal mice when eating high-fat food.

Contradicts the General View

The result challenges the general view of NAMPT, which is largely seen as an enzyme that should be boosted for therapeutic purposes.

'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. We similarly find that NAMPT is critical for fat tissue function. 

"Unfortunately, that function is efficiently storing 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 Associate Professor Zachary Gerhart-Hines from the Novo Nordisk Foundation Center for Basic Metabolic Research and corresponding author on the study.

He does not necessarily believe that generally decreasing NAMPT is a viable treatment strategy in humans. There would be too great a risk for potentially harmful consequences in other tissues of the body.

However, he suggests that this study may pave the way for more research into how NAMPT is linked to the storage of fat from the food we eat. By learning biologically how we become obese in the first place, he hopes that it will eventually be possible to target one of the underlying mechanisms in humans to treat obesity and metabolic disease.