Possible molecular mechanism behind gastric bypass surgery identified

Gastric bypass surgery is one of the most successful weight-loss interventions for treating obesity. Now, by performing the surgery on rats, scientists at Leipzig University have identified a molecular pathway between the gut and the brain that may explain the surgery’s underlying success.

Gastric bypass surgery reroutes the intestines and creates a much smaller stomach pouch, making patients feel full faster. When Wiebke K. Fenske and colleagues performed the surgery on rats, not only did the rodents lose weight, they also preferred low-fat foods to high-fat foods.

At the same time, Fenske’s team saw that the surgery increased synthesis of oleoylethanolamide (OEA) in the intestines, a change they believe is responsible for the weight loss and behavior shift. OEA is a lipid that binds the α-type peroxisome proliferator-activated receptor (PPAR-α), which helps absorb, store, and use fat. When the researchers chemically inhibited PPAR-α in rats that had undergone surgery, their preference switched from a low-fat diet to a high-fat one (Cell Metab. 2017, DOI: 10.1016/j.cmet.2016.12.006).

The team also showed that the OEA pathway connects the gut to the brain via the vagus nerve, and that severing that nerve or blocking downstream dopamine receptors in the brain caused the rats to return to their high-fat-preferring ways.

Hans-Rudolf Berthoud of Louisiana State University says that although the research demonstrates lots of interesting changes in the rats’ physiology, “The question is, which changes are important?” Many pathways are being studied as the basis for obesity beyond OEA, he notes.

Daniele Piomelli of the University of California, Irvine, says if the study is “confirmed in humans, it would provide a mechanistic basis for the therapeutic effects of bariatric surgery. It does not need to be the only basis, of course, but could be an important one.”