Effects of Metformin on the Adaptive Memory Response to Influenza in Obese Individuals Public Deposited

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Last Modified
  • March 22, 2019
Creator
  • Rezk, Omar
    • Affiliation: Gillings School of Global Public Health, Department of Nutrition
Abstract
  • Obesity has reached epidemic proportions in the United States over the past few decades and now affects more than one-third of the adult population. In recent years, obesity has been linked to increased risk of morbidity and mortality from influenza infection. The influenza vaccine is the most effective way to prevent infection with the influenza virus, however, despite vaccination, obese individuals have twice the risk of influenza or influenza-like-illness. Obesity has been shown to impair T cell activation and function. What is not known is how obesity causes the dysfunction. Recent studies have demonstrated that T cell function is heavily reliant on cellular metabolism and T cells will switch their metabolic profile in response to extracellular stimuli. Inflamed visceral adiposity, caused by inflammatory cells infiltrating hypertrophic adipose tissue, is a major hallmark of obesity. Visceral adipocytes of obese individuals release high levels of leptin and other pro-inflammatory cytokines into the serum. These changes in the extracellular environment of T cells may influence their metabolic profile and in turn, impair their function. Therefore, we hypothesized that the metabolic drug metformin would improve T cell function. We show that, compared to obese adults, influenza-vaccinated obese adults prescribed metformin have improved CD8+ memory T cell responses to in vitro challenge with influenza virus. T cells of obese metformin-treated adults express higher levels of activation and functional markers. These results suggest that metformin may help to restore memory T cell function and act as an immunoenhancing agent for obese individuals at the time of vaccination. Further investigation into the metabolic effects of metformin on T cells is needed to uncover the mechanism(s) for metformin-driven improvements in memory T cell function.
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Advisor
  • Coleman, Rosalind
  • Hursting, Stephen
  • Beck, Melinda A.
Degree
  • Master of Science
Degree granting institution
  • University of North Carolina at Chapel Hill
Graduation year
  • 2018
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