Date of Award
Bachelor of Science
metabolic, patients, levels, cortisol, obesity
A diagnosis of Metabolic Syndrome (MSX) requires patients to present with three or more of the following symptoms: elevated fasting blood glucose levels, elevated serum triglyceride levels, low serum HDL levels, elevated blood pressure, and truncal obesity. This pathology shares many similarities with Cushing’s Syndrome (CS) but a diagnosis of CS requires hypercortisolemia. This similarity has led our lab and others to hypothesize that MSX may be a Cushingoid-like state caused by hypersensitivity of the glucocorticoid receptor (GR), a nuclear hormone receptor that is activated when cortisol binds, and or hyperactivity of the enzyme 11beta-hydroxysteroid dehydrogenase (11?- HSD) type 1, the cortisol reductase enzyme. The 11-HSD1 enzyme is responsible for the conversion of inactive cortisone to cortisol, and works primarily in the adipose tissue. Using an allele specific polymerase chain reaction (PCR) protocol, previous research in our lab has found significant correlations between the BclI and N363S polymorphisms of the glucocorticoid receptor and altered patient metabolic profiles in a population of patients seeking bariatric surgery, suggesting their possible contribution to diseases such as obesity and Metabolic Syndrome. Recent work within our lab has found that the frequency of the single nucleotide polymorphism rs12086634, the hyperactivity polymorphism of interest within the 11- HSD1 enzyme, is 23.9% for our obese population and only 14.1% for our random college population. This suggests that this polymorphism may contribute to increased obesity and the MSX metabolic profile by increasing the localized cortisol in adipose tissue. Additionally, our lab has expanded our study to include the cortisol resistance polymorphism TthIIIi (rs10052957) to test the hypothesis that there would be a decreased prevalence of this polymorphism in our subject population. The TthIIIi allele is present at 1.7% frequency in an obese population and at 6.94% frequency in a random college population. Greater understanding of the interplay between these single nucleotide polymorphisms can help physicians and patients make more informed decisions about treatment options for obesity and metabolic syndrome.
Godlewski, Brianna, "The Linkage Between HPA Axis Dysregulation and Metabolic Syndrome" (2017). Honors Theses. 248.