A drug that appears to target specific intestinal bacteria in mice may lead to new treatments for obesity and diabetes in humans.
Mice fed a high-fat diet and provided tempol, an antioxidant drug that may also help protect people from the effects of radiation, were significantly less obese than those that did not receive the drug.
“The two interesting findings are that the mice that received tempol didn’t gain as much weight and the tempol somehow impacted the gut microbiome of these mice,” says Andrew Patterson, assistant professor of molecular toxicology at Penn State.
“Eventually, we hope that this can lead to a new line of therapeutics to treat obesity and diabetes.”
The microbiome is the biological environment of microorganisms within the human body.
Tempol reduces some members of a bacteria—a genus of Lactobacillus—in the guts of mice. When the Lactobacillus levels decrease, a bile acid—tauro-beta-muricholic acid—increases. This inhibits FXR, farnesoid X receptor, which regulates the metabolism of bile acids, fats, and glucose in the body.
“The study suggests that inhibiting FXR in the intestine might be a potential target for anti-obesity drugs,” says Frank J. Gonzalez, laboratory metabolism chief of the National Cancer Institute.
Tempol may help treat type 2 diabetes symptoms. In addition to lower weight gain, the tempol-treated mice on a high-fat diet had lower blood glucose and insulin levels.
“Previously, Dr. (James) Mitchell observed a significant difference in weight gain in mice on tempol-containing diet,” Patterson says. “He approached us to help figure out what was going on, and it had been an interesting journey wading through the complexities of the microbiome.”
Mitchell is radiation biology branch chief at the National Cancer Institute.
Other studies have hinted at the relationship between tempol, the gut microbiome, and obesity, but did not focus on why the drug seemed to control weigh gain, Patterson says.
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