Trimming the stomach lining to fight fat

The importance of the gastric mucosa in regulating metabolism and satiety has been overlooked, according to new research that highlights the stomach lining as a possible target in treating obesity and related disorders. 

Vivek Kumbhari of the Johns Hopkins Medical Institutions in the US, Andreas Oberbach of the Fraunhofer Institute for Cell Therapy and Immunology in Germany, and colleagues carried out the research in an effort to improve obesity treatment.  

Surgeries designed to treat obesity, known as bariatric surgeries, are invasive and expensive, making patients wary of them despite their efficacy. “As a clinician, it’s frustrating to have something that works but that’s not well received by patients,” says Kumbhari. 

Patients usually lose weight and experience rapid improvements in their metabolic profile after a bariatric procedure known as vertical sleeve gastrectomy (VSG), in which most of the stomach is removed. While the dominant view is that bariatric surgeries work by reducing the volume of the stomach, Kumbhari and Oberbach weren’t convinced. 

“Making the stomach smaller helps you lose weight,” says Kumbhari, “but it's not achieving the real goal, which is improving your metabolic profile. When you're treating a patient, what you care about is the metabolic profile. That's why you want them to lose weight.” In other words, the real goal should be to improve patients’ insulin activity, cholesterol levels, blood sugar, and similar factors. Based on a survey of the surgical literature, Kumbhari hypothesized that VSG might work because it removes part of the stomach lining known as the gastric mucosa, which secretes hormones that regulate our appetite and metabolism. 

To test this hypothesis, Kumbhari and Oberbach fattened four-week-old rats by feeding them a high fat diet for eleven weeks before burning away their gastric mucosa. Measurements over the next eight weeks revealed decreased weight and appetite along with improved metabolic profiles in rats subjected to the new procedure known as GMD.  

Remarkably, rats that underwent VSG and GMD had similar metabolic profiles, despite the GMD rats having no change made to the size of their stomach. “We think one of the big components making VSG effective is its removal of the gastric mucosa,” says Kumbhari, although he emphasizes that the results don’t mean that GMD should replace VSG, but rather that the less invasive alternative deserves further investigation.  

The team has since published a follow-up study in pigs, and human trials are scheduled to start this year. “The gastric mucosa is an overlooked organ,” says Kumbhari. “It has a role to play in obesity, food intake and metabolic profile, and it should no longer be ignored. Let's see what it's doing, how it's doing it, and how treating it might be beneficial.”

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