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Biological Chemistry

Acetate’s unexpected role in obesity

Gut microbiome in rodents makes the small molecule, which promotes fat storage and increased appetite, study shows

by Sarah Everts
June 9, 2016 | A version of this story appeared in Volume 94, Issue 24

Image of a fat rat.
Credit: Wikimedia Commons
The gut microbiomes of rodents eating high-fat diets produce acetate, which drives obesity, a new study suggests.

Eating a high-fat diet certainly puts people at risk for obesity, but diet is not the only driver of corpulence. In recent years, scientists have also shown that the gut microbiome is also a culprit in weight gain.

Working with rats and mice, researchers have now found that the unexpectedly modest molecule acetate is at the center of one mechanism by which gut microbes and high-fat diets work in concert to promote obesity (Nature 2016, DOI: 10.1038/nature18309).

If the results hold true for humans, medical researchers may want to develop drugs that interfere with the acetate-based system to help people lose weight.

In a suite of experiments, a team of researchers led by Yale University’s Gerald I. Shulman showed that the gut microbiome in rodents fed high-fat diets produces increased levels of acetate, which then leaves the digestive system and enters the bloodstream. When the acetate reaches the brain, it activates the parasympathetic nervous system, a nerve network responsible for the body’s unconscious actions, including breathing, heartbeats, and, importantly, digestion.

Activation of the parasympathetic nervous system likely drives obesity in two ways, the researchers note: first, by directing the pancreas to increase insulin production, which promotes fat storage, among other things, and second, by increasing levels of the “hunger hormone” ghrelin, also recently implicated in fat storage. This in turn triggers increased feeding, leading to a positive feedback loop for further acetate production by gut microbes.

These results will spawn a lot of follow-up research, says the University of Geneva’s Claes B. Wollheim, who wrote a commentary associated with the new paper (Nature 2016, DOI: 10.1038/534185a). Wollheim told C&EN that he would like to see more work to unravel why certain gut microbes produce a lot of acetate. He’d also like to see follow-up work comparing gut microbiome acetate production with microbial production of propionate, a chemically similar molecule that other researchers have found to promote weight loss and healthy metabolism in rodents (Cell 2014, DOI: 10.1016/j.cell.2013.12.016).

Of course, all this work is moot if it doesn’t apply to humans, Wollheim cautions, but one easy way to evaluate this is to check whether obese people have higher levels of circulating acetate compared with lean people.



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