April 7, 2014

New Insights Into Bariatric Surgery for Obesity

Bathroom scale.

Researchers found that a bariatric surgical procedure reduces obesity and improves glucose tolerance in mice by increasing bile acids and altering gut microbes. The finding hints at new targets for non-surgical interventions to treat obesity.

Bariatric surgeries—operations that alter the stomach, intestines, or both—are among the most effective treatments for severe obesity. The surgeries are thought to lead to weight loss and improvements in related health conditions, such as type 2 diabetes, by reducing the size of the stomach so that less food can be consumed. There are several different types of bariatric operations. Some also alter how food is digested, further decreasing the absorption of calories and nutrients.

Many of the metabolic improvements seen after bariatric operations occur before substantial weight loss, suggesting that other processes may be involved. A team of researchers led by Drs. Karen Ryan and Randy Seeley at the University of Cincinnati set out to investigate how bariatric procedures lead to health benefits. The research was funded in part by NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Heart, Lung, and Blood Institute (NHLBI). Results appeared online on March 26, 2014, in Nature.

In vertical sleeve gastrectomy (VSG), about 80% of the stomach is removed. This creates a gastric “sleeve” that connects the esophagus and small intestine. VSG is known to increase circulation of bile acids. The bile acids bind to farsenoid-X receptor (FXR), a receptor in the nuclei of cells that regulates gene expression.

To test whether the effects of VSG surgery are mediated by FXR, the team created mice that lacked the receptor. These mice and their normal littermates were fed a high-fat diet to induce obesity. They then underwent VSG or sham surgery.

The researchers found that after VSG, the obese mice lost weight and had improved glucose tolerance, as expected. These mice also exhibited a change in the composition of microbes in their gut. In mice that lacked FXR, however, the ability of bariatric surgery to reduce body weight and improve glucose tolerance was substantially reduced.

The findings suggest that the beneficial effects of VSG didn’t result just from the mechanical restriction imposed by a smaller stomach. The surgery also increased circulating bile acids and induced changes in the gut microbial community via FXR signaling pathways.

“There are not enough surgery tables or surgeons to treat the obesity epidemic, so we need to understand how bariatric surgery works so that we can offer more scalable solutions,” Seeley says. “Manipulating the gut bacteria is another way we think that we might be able to mimic how surgery works without having to do the cutting and stapling.”

—by Carol Torgan, Ph.D.

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References: FXR is a molecular target for the effects of vertical sleeve gastrectomy. Ryan KK, Tremaroli V, Clemmensen C, Kovatcheva-Datchary P, Myronovych A, Karns R, Wilson-Pérez HE, Sandoval DA, Kohli R, Bäckhed F, Seeley RJ. Nature. 2014 Mar 26. doi: 10.1038/nature13135. [Epub ahead of print]. PMID: 24670636.

Funding: NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Heart, Lung, and Blood Institute (NHLBI); UNIK Food Fitness and Pharma for Health and Disease research programme; the Torsten Söderberg and NovoNordisk foundations; and Ethicon Endo-Surgery.