Stomach-Specific Protein May Be Key to Fighting Obesity

Models without the Gastrokine-1 protein weigh less and had lower levels of total body fat, despite consuming the same amount of food.

New research published in Scientific Reports suggests that a protein produced exclusively in the stomach plays a major role in the progression of obesity.

The Gastrokine-1 (GKN1) protein is produced abundantly in the stomach, and previous research suggests that it is resistant to digestion, allowing it to pass into the intestine and interact with microbes in the gut. The investigators’ new findings could aid in the development of therapeutics that may help individuals struggling with achieving and maintaining weight loss.

“While diet and exercise are critical to maintaining a healthy weight, some individual struggle with weight loss—even in cases of bariatric surgery, maintaining weight loss can be a challenge,” said co-author David Boone, PhD, an associate professor of microbiology and immunology at the Indiana University School of Medicine, in the press release. “These results are an example of how a better understanding of the gut microbiome and the physiological aspects of obesity—how our bodies regulate metabolism and accumulate body fat—could help inform new therapies.”

Data from the CDC show that adult obesity rates have increased to 42.4% in the United States. In addition to increasing the risk of stroke, diabetes, certain cancers, and other health issues, obesity can also increase the risk of severe illness due to COVID-19. According to the new research, inhibiting the GKN1 protein produced significant differences in weight and levels of body fat in comparison to when the protein was expressed.

The investigators conducted a microbiome analysis of mouse models with and without the GKN1 protein expressed. They measured food intake, caloric extraction, blood sugar, insulin, and triglyceride levels, and used magnetic resonance imaging to monitor body composition. The investigators also calculated energy expenditure and observed inflammation levels.

According to the study, models without GKN1 weighed less and had lower levels of total body fat and higher percentages of lean mass, despite consuming the same amount of food. When put on a high-fat diet, the models without GKN1 showed a resistance to weight gain, increased body fat, and hepatic inflammation. Finally, the researchers found no evidence of adverse effects such as cancer, diabetes, loss of appetite, malabsorption, or inflammation, and results were consistent in male and female models.

Although more research is necessary to determine the efficacy of blocking GKN1 to prevent obesity, the investigators said that such therapies could reduce the burden on health care systems and help improve quality of life for patients if they were proved as a viable solution.

REFERENCE

Your Stomach May Be the Secret to Fighting Obesity [news release]. Indiana University School of Medicine; May 4, 2021. https://medicine.iu.edu/news/2021/05/Your-stomach-may-be-the-secret-to-fighting-obesity. Accessed May 10, 2021.