Abstract
Purpose: Dietary and exercise interventions have the potential to modify thyroid hormone levels in individuals with obesity. This study investigates the specific mechanisms through which these interventions influence thyroid function, employing a multiomics approach. Methods: 16 volunteers with obesity participated in a two-week regimen of aerobic exercise combined with dietary control. Fasting blood samples and anthropometric measurements were taken before and after the intervention. Serum untargeted lipidomics and metabolomics analyses were performed, alongside evaluations of serum thyroid hormone levels. Additionally, an RNA sequencing dataset was obtained which included gene expression data for skeletal muscle and subcutaneous fat both prior to and following weight loss. Results: Following the intervention, significant alterations were observed in serum levels of thyroid hormones, lipid molecules, and metabolites among participants. Notably, there was a substantial reduction in the levels of tyrosine and phenylalanine (p < 0.001). Furthermore, this intervention had a pronounced effect on the activity of thyroid hormone signaling pathways. Conclusion: Dietary modifications along with exercise facilitate the restoration of thyroid function by enhancing the consumption of tyrosine and phenylalanine while concurrently altering the activity within thyroid hormone signaling pathways. These findings provide valuable insights into potential treatments for obesity-related thyroid dysfunction. Trial Registration: Chinese Registry of Clinical Trials: ChiCTR2000040981.