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Biological Chemistry

Harnessing The Microbiome To Curb Hunger

ACS Meeting News: Microbes genetically engineered to produce appetite-suppressing chemicals keep mice slim

by Bethany Halford
March 26, 2015 | A version of this story appeared in Volume 93, Issue 13

Credit: Shutterstock
Mice slim down with N-acylethanolamine-making bacteria.
Photo of a mouse inside a tape measure.
Credit: Shutterstock
Mice slim down with N-acylethanolamine-making bacteria.

There’s a new front in the battle of the bulge. Scientists think reprogramming microbes in our guts might be the secret to achieving a slim stomach.

Last year, researchers led by Vanderbilt University’s Sean S. Davies showed that mice fed bacteria genetically engineered to produce N-acylphosphatidylethanolamines, or NAPEs, stayed slimmer on a high-fat diet compared with mice that were fed different bacteria or none at all.

NAPEs are produced naturally in the small intestine after food consumption and have been linked to feelings of fullness. “It appears that people who are obese don’t make enough of those compounds in response to food, and that may be one of the reasons they tend to overeat,” according to Davies.

There is, however, some debate as to whether the NAPEs themselves are responsible for suppressing appetites. Some scientists think N-acylethanolamines (NAEs), which are produced when enzymes in the small intestine break down NAPEs, actually curb hunger.

Davies reasoned he could answer this question by creating bacteria that produce NAEs and comparing them with his NAPE-producing bacteria. In normal mice, he found that both NAPE- and NAE-producing microbes had similar slimming effects. But in mice that lacked the enzyme that converts NAPEs to NAEs, only the NAE-producing bacteria kept the mice thin.

That result suggests that NAEs are really responsible for appetite suppression, and bacteria that produce them directly could be considered for curbing obesity, Davies said during a presentation in the Division of Medicinal Chemistry last week at the American Chemical Society national meeting in Denver.

Steven M. Firestine, a pharmaceutical sciences professor at Wayne State University, commented, “Despite its importance in human diseases such as obesity, our ability to control hunger and satiety has been limited.” Davies’s work, he said, provides an interesting approach to this problem. “Although much work must be done to prove the efficacy and safety of this system,” Firestine said, “the approach taken by Davies has the potential to provide a long-term solution for the treatment of obesity in humans.”



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