GLP-1 Therapy and NK Cell Functionality in Obesity

Therapy with glucagon-like peptide-1 (GLP-1) analogues may restore natural killer (NK) cell functionality in people with obesity, contributing to their ability to fight off cancer, researchers suggest in a recent study published in Obesity. The study findings will be presented at the 30th European Congress on Obesity on the 20th of May in Dublin.

Obesity is associated with increased mortality from viral infection and cancer. Peripheral blood natural killer cells are defective in obese people. "Our study showed that GLP-1 analogues can restore the function of natural killer cells in the body, including its ability to kill cancerous cells," the authors wrote.

In the study, semaglutide (GLP-1 therapy) improved NK cell function, as measured by interferon-γ/granzyme B production and cytotoxicity. In addition, the results revealed increases in a CD98-mTOR-glycolysis metabolic axis, which is critical for producing NK cell cytokine.

Previous research has shown that obese people have functionally defective natural killer cells with a reduced capacity for cytokine production and kill target cells underpinned by impaired cellular metabolism. The researchers said, "It is plausible that changes in peripheral NK cell activity contribute to multimorbidity, including an increased cancer risk in obese people."

Conor De Barra, Maynooth University, County Kildare, Ireland, and colleagues aimed to determine whether therapy with long-acting GLP-1 analogues, an effective obesity treatment, could restore NK cell functionality in people with obesity.

In a cohort of 20 people with obesity, the researchers investigated whether six months of once-weekly GLP-1 therapy (semaglutide) restores natural human killer cell function and metabolism using cytotoxicity assays, enzyme-linked immunosorbent assays, and multicolour flow cytometry.

Study Findings

• People with obesity who received GLP-1 treatment have improved natural killer cell function, as measured by cytotoxicity and interferon-γ/granzyme B production.
• The study demonstrates an increased CD98-mTOR-glycolysis metabolic axis, critical for NK cell cytokine production.
• The reported NK cell function improvements appear independent of weight loss.

The results imply that NK cell functionality is restored in people with obesity following glucagon-like peptide-1 analogue treatment. GLP-1 therapy boosts the cellular metabolism of natural killer cells in these patients. These treatment-related improvements in NK cells were independent of weight loss.

"The direct restoration, by GLP-1 therapy, of NK cell cytokine production and metabolism in PWO may contribute to the overall benefits seen with this class of medication," the authors concluded.

Reference

Barra, C. D., Khalil, M., Mat, A., Shaamile, F., Brennan, K., & Hogan, A. E. Glucagon-like peptide-1 therapy in people with obesity restores natural killer cell metabolism and effector function. Obesity. https://doi.org/10.1002/oby.23772