Circulating MOTS-c Levels Significantly Reduced in Hashimoto's Thyroiditis, Linking Mitochondrial Dysfunction to Autoimmunity and Insulin Resistance

Hashimoto's thyroiditis (HT) is a prevalent autoimmune disorder characterized by chronic inflammation and metabolic alterations, for which current standard-of-care with levothyroxine primarily addresses thyroid hormone levels but not the underlying autoimmunity or systemic symptoms. Mitochondria-derived peptides (MDPs) like MOTS-c have emerged as crucial regulators of cellular metabolism, insulin sensitivity, oxidative stress, and inflammatory responses. Investigating MOTS-c in HT could reveal a key link between metabolic dysregulation and immune dysfunction, offering insights into novel therapeutic or diagnostic strategies beyond hormone replacement.

This cross-sectional study compared 90 patients diagnosed with Hashimoto's Thyroiditis (HT) to 90 age- and sex-matched healthy controls. Researchers measured circulating MOTS-c levels in all participants. Additionally, they assessed various metabolic parameters including body mass index (BMI), fasting glucose, HbA1c, and HOMA-IR, alongside inflammatory markers like C-reactive protein (CRP) and thyroid autoantibody levels. Multivariable regression analysis was performed to identify independent determinants of MOTS-c concentrations, and subgroup analyses explored associations within the HT cohort.

A total of 180 participants were included, comprising 90 HT patients and 90 healthy controls. Circulating MOTS-c levels were significantly lower in patients with HT compared to controls (p < 0.001). MOTS-c levels demonstrated significant inverse correlations with several key metabolic and inflammatory markers: body mass index, fasting glucose, HbA1c, HOMA-IR, thyroid-stimulating hormone (TSH), C-reactive protein (CRP), and thyroid autoantibody levels (all p < 0.05).