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Bypass surgery

Bariatric surgery improves vagal neuronal signals

The results may also better predict which patients will keep the weight off after surgery

Researchers from Penn State College of Medicine have shown how gastric bypass surgery restores some properties of vagal neuronal signals that help regulate the digestive system, which could lead to new treatments that produce the same results without surgery. The results may also better predict which patients will keep the weight off after surgery.

It is known that diabetes can resolve before weight is lost, and sometimes before the person even leaves the hospital after gastric bypass surgery.

"We know gastric bypass improves the health of nerve cells and reverses the effects on the signals,” said Kirsteen Browning, assistant professor of neural and behavioral sciences. "Even if the nerve cells have been affected over a long term, gastric bypass still improves toward normal function. This suggests an altering of the neural signals from the gut to the brain and back.”

Kirsteen Browning assistant professor of neural and behavioral sciences

These nerve cells send signals to tell the body's digestive system how to respond properly and regulate normal functions of digestion. In obese people, the nerve cells are less excitable, meaning they respond less to normal stimulation.

"These signals tell you to stop eating," said study co-author Andrew Hajnal, professor of neural and behavioral sciences. "Obviously these signals are strong enough to be overcome by all of us and we can eat more even after we are told we are full. However, as obesity develops, it appears these signals are less strong and easier to overcome.

Study

In the study, which is published in the Journal of Physiology, the investigators assessed whether  high-fat diet-induced obesity also affects the properties of vagal efferent motoneurones and whether these effects were reversed following weight loss induced by Roux-en-Y gastric bypass.

They took whole-cell patch-clamp recordings from rat dorsal motor nucleus of the vagus (DMV) neurones in thin brainstem slices and reported that DMV neurones from rats exposed to high-fat diet for 12–14 weeks were less excitable, with a decreased membrane input resistance and decreased ability to fire action potentials in response to direct current pulse injection.

They also found that the DMV neurones were also less responsive to superfusion with the satiety neuropeptides cholecystokinin and glucagon-like peptide 1. However, Roux-en-Y gastric bypass reversed all of these diet-induced obesity effects.

Although diet-induced obesity also affected the morphological properties of DMV neurones (increasing their size and dendritic arborisation), RYGB did not reverse these morphological alterations.

“Remarkably, independent of diet, RYGB also reversed age-related changes of membrane properties and occurrence of charybdotoxin-sensitive (BK) calcium-dependent potassium current,” the authors write. “These results demonstrate that diet-induced obesity also affects the properties of central autonomic neurones by decreasing the membrane excitability and pharmacological responsiveness of central vagal motoneurones and that these changes were reversed following RYGB.”

However, they noted that in contrast diet-induced obesity changes in morphological properties of DMV neurones were not reversed following gastric bypass surgery, suggesting that they may be due to diet, rather than obesity.

Conclusions

“These findings represent the first direct evidence for the plausible effect of RYGB to improve vagal neuronal health in the brain by reversing some effects of chronic high-fat diet as well as ageing,” the authors conclude. “Vagovagal neurocircuits appear to remain open to modulation and adaptation throughout life, and understanding of these mechanisms may help in development of novel interventions to alleviate environmental (e.g. dietary) ailments and also alter neuronal ageing. “

"Once we understand what gastric bypass is doing, we hope we can mimic that with other treatments," said Browning. "Restricting the size of the stomach may not be the major player of the surgery; restoring normal neural function is also an important aspect."

Scientists may also be able to determine why the surgery is unsuccessful for some patients and better determine if surgery is the best option.

"Gastric bypass surgery doesn't work in all people," Hajnal said. "Some people regain the weight, but we don't know why. By understanding this happens, we may be able to predict in advance which patients will respond to the surgery."

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