Investigating The Role of Single Nucleotide Polymorphisms Associated With Cortisol Activity in Metabolic Syndrome and Post-Bariatric Surgery Weight Loss Success

Obesity, a disease of excess adipose tissue, affects millions of people worldwide; in 2022, approximately one in eight individuals were living with obesity. Adult obesity rates have more than doubled since 1990 and adolescent obesity rates have quadrupled. Obesity has various subtypes including those driven by imbalances in hormones like cortisol. The health complications of obesity include an increased risk of type 2 diabetes, cardiovascular disease, stroke, and certain cancers. The body's stress response can play a critical role in obesity. Chronic stress leads to sustained activation of the hypothalamic-pituitary-adrenal (HPA) axis resulting in elevated cortisol production. In addition to obesity, excess cortisol can result in high blood pressure, type 2 diabetes, and altered lipid profiles (including high triglycerides and low HDL). The obesity seen in the presence of excess cortisol is a very specific type of obesity called centripetal obesity with a high level of visceral adipose tissue (VAT) around internal organs in the abdominal cavity. Many of these symptoms are shared with a specific subtype of obesity known as metabolic syndrome (MetS). However, patients with MetS do not have elevated cortisol levels, suggesting that their bodies are more sensitive to cortisol which is then contributing to their MetS. Bariatric surgery is the most effective treatment for obesity. Unfortunately, it does not always work for everyone. It is important to explore why some lose significant amounts of weight while others do not. A possibility is that patients for whom bariatric surgery is not successful have altered cortisol sensitivity that reduces the efficacy of the surgery. Past research has indicated there are single nucleotide polymorphisms (SNPs), found in genes associated with the regulation and action of cortisol in the body. A total of eight SNPs were investigated in two genes, 11B-HSD1 and NR3C1. We hypothesized that the presence of these SNPs is associated with the development of MetS and with lower weight loss after bariatric surgery. Buccal swabs were used to collect DNA from patients with obesity being seen at the Ellis Hospital Bariatric Care Center and then qPCR was used to determine allele frequencies for the various SNPs. Since obesity rates in the US have jumped from 13% to 40% in the last 50 years and continue to increase, identifying genetic markers linked to MetS or weight loss success could help identify ways to predict or treat obesity.