Kidney Week

Abstract: FR-PO1120

Systemic MOTS-c Levels Are Increased in Adults with Obesity in Association with Metabolic Dysregulation and Remain Unchanged After Weight Loss

Session Information

• Health Maintenance, Nutrition, and Metabolism
  November 07, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Health Maintenance, Nutrition, and Metabolism

• 1500 Health Maintenance, Nutrition, and Metabolism

Authors

• Yoon, Se-Hee, Mayo Clinic Minnesota, Rochester, United States

Se-Hee Yoon, MD, PhD

• Yuan, Fei, Shanghai Jiao Tong University, Shanghai, China

Fei Yuan, MD

• Zhu, Xiang yang, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Xiang yang Zhu, MD, PhD

• Tang, Hui, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Hui Tang

• Eirin, Alfonso, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Alfonso Eirin, MD

• Lerman, Amir, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Amir Lerman, MD

• Cohen, Pinchas, University of Southern California Leonard Davis School of Gerontology, Los Angeles, California, United States

Pinchas Cohen, MD

• Lerman, Lilach O., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Lilach O. Lerman, MD, PhD, FASN

Background

MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) is a mitochondrial-derived peptide recently recognized as an important regulator of metabolic homeostasis. Although its role in glucose and lipid metabolism is emerging, changes in circulating MOTS-c associated with obesity remain unclear.We tested the hypothesis 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 immunohistochemistry in samples from 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<0.01). BMI and HOMA-IR independently predicted elevated MOTS-c levels. MOTS-c showed a biphasic relationship with HOMA-IR, rising sharply above HOMA-IR of ~6.6 mmol/L×µU/mL. Similarly, MOTS-c increased linearly with BMI up to ~34.6 kg/m², but then declined at higher BMIs. Adipose tissue MOTS-c expression did not differ between the groups, or correlated with circulating MOTS-c. Despite significant BMI improvements post-surgery (P<0.001), circulating MOTS-c levels remained unchanged (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.

Fig. 1. Circulating MOTS-c and metabolic indices.
(A) Plasma MOTS-c in lean (BMI<30) vs. obese (BMI≥35).
(B-C) Biphasic MOTS-c vs. BMI (~34.6) and HOMA-IR (~6.6).
***P<0.001.

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025f05xxhks