Investigating the potential role of T helper 17 cells among women experiencing overweight and obesity and their possible therapeutic targeting of the RORγt molecule

Obesity is a growing healthcare problem globally. In Saudi Arabia, 24% of adults aged 15 years and above have been living with Obesity. It is considered a chronic inflammatory condition that is linked to a wide range of disorders including type 2 diabetes mellitus, insulin resistance and cardiovascular diseases. In this study, we aimed to assess the influence of obesity on the proportion of Th17 cells among healthy, overweight, and obese women in Saudi Arabia. Additionally, we aimed to explore potential ligands targeting the master transcription factor of Th17 cells: RORγt. A cross-sectional study was conducted, wherein their body mass index (BMI) and waist circumference (WC) were measured. The proportion of peripheral Th17 cells was determined using flow cytometry. We found a decrease in the proportion of peripheral Th17 among women with central obesity, though this was observed among overweight and obese participants. Interestingly, both BMI and WC were inversely correlated with the proportion of peripheral Th17 cells in women experiencing overweight or obesity, while no change was observed among healthy participants. Notably, the analysis revealed a significant moderate negative correlation between the proportion of Th17 cells and HbA1c levels, observed only among the overweight and obese participants. In this study, we identified three potential binding sites on RORγt molecules of Th17 cells, bound to 58 chemical ligands. The majority of the chemical structures (72.4%) were targeted binding pocket 1 of the RORγt molecule. These findings could provide a new insight to develop new pharmaceutical molecules targeting immune cells to combat obesity and related metabolic disorders.