Systemic MOTS-c levels are increased in adults with obesity in association with metabolic dysregulation and remain unchanged after weight loss.
This observational study investigated circulating levels of MOTS-c — a mitochondrial-derived peptide involved in metabolic regulation — in adults with and without obesity, and examined whether levels changed after bariatric surgery. Researchers compared 22 lean controls with 32 obese participants scheduled for bariatric surgery, measuring MOTS-c concentrations alongside metabolic and inflammatory markers. A subset of 10 obese patients was followed longitudinally before and 6 months after surgery. Adipose tissue MOTS-c expression was also assessed via immunofluorescence in lean (n=6) and obese (n=14) subjects. The study found that circulating MOTS-c was significantly higher in obese versus lean individuals (273 vs. 223 pg/mL), and positively correlated with BMI and HOMA-IR. A notable biphasic relationship emerged between MOTS-c and HOMA-IR, with a sharp rise above a threshold of ~6.6 mmol/L×µU/mL. Despite significant weight and BMI reductions following bariatric surgery, MOTS-c levels did not change significantly post-operatively. Adipose tissue expression did not differ between groups. The authors suggest MOTS-c may reflect a compensatory metabolic response in obesity and insulin resistance. Key limitations include the small sample size, particularly in the longitudinal substudy, and the lack of an independent validation cohort.
Why this grade: While conducted in humans, the study is observational with a small sample size (n=54 cross-sectional; n=10 longitudinal) and lacks a control group for the surgical intervention, limiting causal inference.
Introduction MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) is a mitochondrial-derived peptide and regulator of metabolic homeostasis. Although its role in glucose and lipid metabolism is emerging, changes in circulating MOTS-c with obesity remain unclear. We hypothesized that circulating MOTS-c concentrations would be altered in obese vs. lean adults in associations with altered metabolic and inflammatory markers. Methods Circulating MOTS-c levels, metabolic parameters, and inflammatory markers were compared between 22 lean controls and 32 obese participants scheduled for bariatric surgery. Longitudinal changes in weight, MOTS-c levels, and metabolic markers were also analyzed in 10 of the obese patients before and 6 months after bariatric surgery. Additionally, adipose tissue MOTS-c expression was assessed by immunofluorescence in lean kidney donors (n = 6) and obese (n = 14) subjects. Results Circulating MOTS-c levels were significantly higher in obese compared to lean individuals (273 ± 56 vs. 223 ± 50 pg/mL; P P = 0.035 and P = 0.032, respectively). MOTS-c showed a biphasic relationship with HOMA-IR, rising sharply above HOMA-IR of ∼ 6.6 mmol/L×µU/mL. Adipose tissue MOTS-c did not differ between the groups or correlate with circulating MOTS-c. Despite significant BMI improvements post-surgery ( P P = 0.913). Conclusion Circulating MOTS-c levels are elevated in obesity, exhibiting a nonlinear relationship with BMI and insulin resistance. MOTS-c may represent a compensatory metabolic response in obesity and insulin-resistant states, highlighting its potential as a clinical biomarker. This preliminary exploratory study warrants validation in larger and independent cohorts.
Educational summary of published research — not medical advice. License: cc by-nc. Full text is shown only where licensing permits.