Obesity-Related Enzyme Targeted in Mouse Study

Findings suggest new way to prompt body to burn extra energy.

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2014-04-10

An enzyme in the fat and liver of mice could take a key role in future attempts to battle obesity and type 2 diabetes, according to a new study.

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The enzyme -- nicotinamide N-methyltransferase, or NNMT -- appears to help regulate the ability of cells to burn energy efficiently, researchers report.

By hampering the gene that produces the enzyme, researchers were able to keep mice fed a high-fat diet from gaining weight. The mice also became better at using insulin to process blood sugar, which could lower their odds for developing diabetes.

"The mice were eating normally. It wasn't a food intake effect. They actually had increased energy expenditure," said expert. "For every calorie they ate, they burned up more energy."

Controlling levels of this enzyme could potentially help people reach and maintain a healthy weight by prompting the body to burn excess energy rather than store it.

Diet and exercise will always be very key, but this opens up the possibility of a new way to speed up cellular metabolism so people don't store as much fat.

Results of animal research do not necessarily apply to humans, however.

Researchers discovered this new role for the enzyme while researching the role of body fat in the development of type 2 diabetes.

Researchers studied thousands of genes present in the fat of mice to determine which ones affected the body's ability to convert glucose (blood sugar) into cellular energy.

The investigators found large amounts of the NNMT enzyme in the fat of mice prone to obesity or diabetes because they used glucose less efficiently and tended to store it away in body fat. This enzyme is already known, but no one has linked it to cellular metabolism.

To test the enzyme's role in weight gain, researchers used a targeted genetic medication in the mice being served a high-fat diet to "knock down" the gene that promotes production of the enzyme.

Reducing levels of the enzyme in their fat and liver protected mice from diet-induced obesity, causing a 47 percent reduction in their body fat and a 15 percent increase in their lean body mass.

Mice with reduced levels of this enzyme also experienced a 50 percent to 60 percent reduction in their blood insulin levels, an indication of improved insulin sensitivity.

Further, the medication worked without causing any harmful side effects.

Researchers believe the enzyme influences metabolism by suppressing a biochemical process known as a "futile cycle," in which cellular reactions are sped up and burn more energy.

Human beings have evolved to have efficient metabolisms so they could survive famines and droughts, and times when food was not available. "A person with a more efficient metabolism is more likely to gain weight than a person with a less efficient metabolism.

Don't expect this new finding to be translated into a weight-control treatment for humans anytime soon, however.

One cannot be assured that this will be a totally healthy thing to do. We don't know what side effects this approach would have. The ability to gain weight on a high-fat diet is a normal part of animal metabolism. Interfering with this natural process could have unintended consequences.

The new research only tested the ability to prevent weight gain by reducing the enzyme's levels in mice. They did not use this drug as a weight-loss measure.

"Most of these kinds of discoveries do not lead to new drugs for one reason or another," expert said. "Even if successful, it will take close to a decade until a drug targeting NNMT reaches our clinics."

Source: U.S. Dept. of Health & Human Services