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Endoscopic ablation reduces ghrelin leading to weight loss

Endoscopic ablation reduces the production of ghrelin, a hormone that triggers hunger, resulting in decreased appetite and significant weight loss, according to a first-in-human trial presented at Digestive Disease Week 2024.

Christopher McGowan

The outcomes made in the presentation, ‘Endoscopic ablation of the gastric fundus in adults with obesity: A first-in-human study’, by Dr Christopher McGowan, a gastroenterologist and medical director of True You Weight Loss, a physician-owned clinic based in North Carolina.

In the procedure, ablation begins when an endoscopist inserts fluid to protect underlying stomach tissues and then uses a tiny device to ablate the mucosal lining of the upper portion of the stomach, known as the gastric fundus. Feelings of hunger originate in the gastric fundus when the chamber empties, leading to increased production of ghrelin. Hunger subsides as the gastric fundus fills with food and ghrelin production dips. Mucosal ablation reduces the number of ghrelin-producing cells.

The six-month trial involving ten female patients with obesity resulted in a 7.7% loss of body weight and a reduction of more than 40% in fasting ghrelin levels. Patients reported through validated questionnaires that their hunger was diminished by more than a third. The procedure also caused a 42% reduction in stomach capacity, according to a standard drink test.

"Obesity is chronic, lifelong disease that is predicted to affect nearly half of the US population by 2030. Its effect on overall health, quality of life, and global health care costs is massive, and we need as many treatment options as possible," said McGowan. "This relatively brief, outpatient, non-surgical procedure can facilitate weight loss and significantly curb hunger, and it could be an additional option for patients who don't want or aren't eligible for anti-obesity medications, such as Wegovy and Ozempic or bariatric surgery."

Previously, the only proven method of reducing ghrelin was to surgically remove or bypass the gastric fundus. There is currently no pharmacologic method of reducing ghrelin. Newer anti-obesity medications, like Ozempic and Wegovy, employ a different hormonal pathway - GLP-1.

"Obesity and weight are very complex and regulated by multiple hormone pathways. This procedure alters one of these many pathways that make it difficult for people to lose weight and maintain weight loss," he added.

Levels of ghrelin are typically higher in patients with obesity and rise when people lose weight for any reason, making it hard to maintain weight loss.

If the procedure is proven effective over longer periods of time and in larger trials, it could complement endoscopic sleeve gastrectomy, a non-surgical weight-loss procedure that reduces the size of the stomach, or it could potentially be offered as a one-time procedure that replaces or complements other treatments, McGowan said.

"This is just the beginning. The first question was whether we can endoscopically reduce hunger and ghrelin. The answer is: yes, we can," he concluded.


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