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Study of Weight Loss Surgery-Induced Remission of Type 2 Diabetes May Lead to New Treatments

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Study of Weight Loss Surgery-Induced Remission of Type 2 Diabetes May Lead to New Treatments
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It’s a known fact that weight loss surgery often causes remission in type 2 diabetes patients. Researchers have now found that a bile acid receptor called TGR5 is an important link to this response. Results of the study were published in the journal Gut, titled TGR5 contributes to glucoregulatory improvements after vertical sleeve gastrectomy in mice.”

While doctors have known that bariatric surgery, an abdominal procedure to help obese people lose weight, often leads to remission of type 2 diabetes, the mechanisms responsible remained a mystery.

A research team at Cornell University in Ithaca, New York, tackled this question by investigating a bile acid receptor called TGR5. It was previously reported that a common bariatric surgery called vertical sleeve gastrectomy (VSG) increases bile acid concentrations, and that bile acid signaling through its receptor, TGR5, improves glucose homeostasis. Researchers investigated the role of this receptor in mediating the regulatory benefits of weight loss surgery.

The researchers performed sham bariatric surgeries in two types of mice: normal mice who were fed high-fat diets (controls), and mice genetically engineered to have no TGR5 receptors — TGR5 knockout mice. While in the VSG surgery mice had part of their stomach removed, only sutures were made in the animals’ stomachs so that researchers could assess and control for the surgical procedure effects. Normal mice submitted to sham surgery were under a restricted high-fat diet so their weight matched those in the VSG group.

The team found that after VSG, mice exhibited increased concentrations of bile acids and had improved fasting glycaemia, glucose tolerance and glucose-stimulated insulin secretion. VSG increased hydrophilic bile acid, the most beneficial type. But the benefits of VSG were lost in the TGR5 knockout mice.

These results suggest that TGR5 has an important contribution in regulating glucose, and may be involved in the shift, after VSG, into beneficial bile acid production.

“In the United States, bariatric surgeries are primarily allowed for obesity treatment, generally requiring a BMI [body mass index] over 40 or a BMI over 35 with significant obesity-related co-morbidities, though some clinicians argue for expanding the use of these surgeries for treatment of diabetes,” Bethany Cummings, assistant professor of biomedical sciences at Cornell’s College of Veterinary Medicine and the study’s lead author, said in a press release. “Our goal is to study these surgeries in order to identify novel therapeutic targets, because surgery is not without risks and a drug is much easier to widely distribute among patients.”

In the future, researchers will explore the functions of TGR5, which may potentially lead to the development of new therapies for type 2 diabetes.

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