Author ORCID Identifier
https://orcid.org/0009-0001-5860-7193
Date Available
1-7-2026
Year of Publication
2026
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
College
Medicine
Department/School/Program
Molecular and Cellular Biochemistry
Faculty
Barbara S. Nikolajczyk
Faculty
M. Paul Murphy
Faculty
Trevor Creamer
Abstract
Type 2 Diabetes (T2D), one of the top ten causes of death worldwide, is fueled by chronic inflammation. T2D is considered a metabolic disease, and there is a great push to target metabolic and associated inflammatory pathways to ameliorate the disease & its comorbidities i.e., obesity and cardiovascular disease. Thus far, clinical trials of anti-inflammatory drugs have had modest impacts on T2D and have not led to changes in clinical practice. This may in part be due to a gap in knowledge in the mechanism(s) driving obesity-associated chronic inflammation. I posit that metabolic abnormalities in immune cells in those with T2D alter their function, thus perpetuating T2D-associated inflammation. Ninety percent of individuals with T2D-associated inflammation are overweight or obese, and over ten percent are morbidly obese, defined as a BMI at or above forty. Bariatric surgery has become a standard treatment for severe/class III obesity that causes significant weight loss, tangentially causing patients’ glycemic control to improve. These surgeries therefore are a viable treatment for obesity-associated T2D. However, weight loss and eventual regain is highly variable among bariatric surgery patients. Bariatric surgery’s effects on immune cells, specifically immune cells in the periphery, is also thus far understudied. Our lab’s work has shown that the progression from normal glucose tolerance (NGT) to T2D is not linear; rather, inflammation changes as an individual shifts to a prediabetes (preT2D) phenotype. We observed unique shifts in cytokine signatures and metabolic preferences in peripheral immune cells from preT2D, NGT, and T2D subjects. Although our prior works did not study class III obesity, the novel findings from these works shaped my central hypothesis that VSG impacts immune cell metabolism and function differently based on T2D status prior to surgery. We analyzed the metabolism of peripheral immune cells through several mechanisms. We first tested live cell metabolic flux to determine rates of glycolysis and oxidative phosphorylation. Finding differences in metabolic pathway preferences among cohorts through this method, we used stable isotope resolved metabolomics (SIRM) as a more granular approach to understand the rates of metabolic reactions via fractional enrichment. This revealed that immune cells from all cohorts had similar enrichment of some metabolites that we probed for i.e., glycolysis intermediates, yet some metabolites involved in the TCA cycle i.e., citrate showed differences among cohorts. From these experiments, we concluded that immune cell metabolism, specifically those involved in energy producing pathways, were similar between NGT and T2D cohorts, and preT2D immune cell metabolism was unique compared to other cohorts. To test immune cell function, we analyzed cytokines secreted by peripheral immune cells after culture and stimulation. We found that immune cell function changed comparing pre- and post-surgery samples within each cohort. We also saw differences between cohorts at each time point, suggesting that both T2D status and bariatric surgery impact. Throughout recruitment of bariatric surgery patients, we discovered that a significant portion of these patients were prescribed a glucagon like peptide 1 (GLP1) receptor agonist. Because of the potentially anti-inflammatory effects of this drug, we analyzed cytokine secretion comparing cells from those who took this drug to those who did not, separating by metabolic status. Preliminary analyses showed no significant differences within this comparison, although more complex analyses are needed to substantiate this claim. My project altogether analyzed inflammation through measuring immune cell function (i.e., cytokine secretion) and immune cell metabolism (i.e., rates of energy-producing pathways and pathway preferences) in bariatric surgery patients with versus without T2D.
Digital Object Identifier (DOI)
https://doi.org/10.13023/etd.2025.574
Funding Information
This study was supported by the Center for Clinical and Translational Sciences training grant (no. UL1TR001998) from 2023 to 2025.
Recommended Citation
Hart, Samantha N., "BARIATRIC SURGERY IMPACTS IMMUNE CELL METABOLISM AND FUNCTION DEPENDENT ON METABOLIC STATUS" (2026). University of Kentucky Doctoral Dissertations. 854.
https://uknowledge.uky.edu/gradschool_diss/854
Included in
Biochemical Phenomena, Metabolism, and Nutrition Commons, Biochemistry Commons, Nutritional and Metabolic Diseases Commons, Other Immunology and Infectious Disease Commons
