Reduced Circulating MOTS-c Levels in Hashimoto’s Thyroiditis Reflect Integrated Autoimmune and Metabolic Dysregulation: A Cross-Sectional Study
Journal of Clinical Medicine, cilt.15, sa.11, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 15 Sayı: 11
- Basım Tarihi: 2026
- Doi Numarası: 10.3390/jcm15114002
- Dergi Adı: Journal of Clinical Medicine
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, EMBASE, Academic Search Ultimate (EBSCO), Health Research Premium Collection (ProQuest)
- Anahtar Kelimeler: Hashimoto's thyroiditis, MOTS-c, mitochondria-derived peptides, autoimmune thyroid disease, immuno-metabolism, mitochondrial dysfunction
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Background: Hashimoto’s thyroiditis (HT) is a common autoimmune disorder characterized by chronic inflammation and metabolic alterations. Mitochondria-derived peptides (MDPs), particularly mitochondrial open-reading frame of the 12S rRNA-c (MOTS-c), have emerged as key regulators of cellular metabolism, insulin sensitivity, oxidative stress, and inflammatory responses. This study aimed to investigate the association between circulating MOTS-c levels and HT and to explore its potential role in thyroid autoimmunity and metabolic regulation. Methods: In this cross-sectional study, patients diagnosed with HT (n: 90) were compared with age- and sex-matched healthy controls (n: 90). Results: A total of 180 participants were included, comprising 90 patients with HT and 90 age- and sex-matched 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 body mass index, fasting glucose, HbA1c, HOMA-IR, thyroid-stimulating hormone, C-reactive protein, and thyroid autoantibody levels (all p < 0.05). In subgroup analyses, these associations remained significant within the HT cohort, particularly for HOMA-IR and thyroid autoantibodies. Multivariable regression analysis identified HT (β = −30.04, p < 0.001) and HOMA-IR (β = −0.85, p < 0.001) as independent determinants of reduced circulating MOTS-c levels. Levothyroxine (LT4) use was not associated with significant differences in MOTS-c concentrations. Conclusions: Circulating MOTS-c levels are markedly reduced in patients with HT and are independently associated with insulin resistance and autoimmune burden. These findings suggest that impaired mitochondrial signaling may play a role in the pathophysiology of thyroid autoimmunity and highlight MOTS-c as a promising biomarker linking metabolic dysfunction and immune dysregulation.