Metabolic/Weight

MOTS-c

Research Reagent · Laboratory Use Only

Quick Answer

What does current research show about MOTS-c peptide and metabolic function?

MOTS-c is a mitochondrial-derived peptide encoded by the 12S rRNA gene. Preclinical research published in Cell Metabolism (Lee et al., 2015) indicates it regulates glucose metabolism, activates AMPK pathways, and may improve insulin sensitivity. Studies in aged mouse models suggest potential roles in metabolic homeostasis and longevity. Human clinical data remain limited.

PMID41945630↗DOI10.1016/j.cmet.2015.01.013↗⟳ Reconstitution Calculator
Scientific AbstractPMID 41945630 · 2026

Objective

MOTS-c is a mitochondria-derived peptide associated with reduced insulin resistance and obesity. The m.1382A>C polymorphism of the MOTS-c gene is linked to an increased risk of type 2 diabetes in men. However, no studies have explored the relationship between this polymorphism and MOTS-c levels in adolescents with polycystic ovary syndrome (PCOS). This study aimed to investigate the differences in MOTS-c levels between adolescents diagnosed with PCOS and those without PCOS, as well as the associations with metabolic parameters. The association between the MOTS-c gene polymorphism and serum MOTS-c levels in adolescents with PCOS was also evaluated. SUBJECTS AND METHODS: Adolescents aged 12-18 diagnosed with PCOS were recruited based on irregular menstrual cycles and clinical/biochemical hyperandrogenism, excluding other conditions. The control group consisted of adolescents with regular menstruation. Serum MOTS-c levels were measured using ELISA, and the m.1382A>C polymorphism was analyzed by sequencing.

Results

The study included 121 adolescents with PCOS and 125 healthy controls. The mean serum MOTS-c levels in the PCOS group were higher than in the control group; however, this difference did not reach statistical significance (p = 0.059). There was no significant association between MOTS-c levels and anthropometric or metabolic parameters within the PCOS group (p > 0.05). All participants had the wild-type (A/A) genotype for the m.1382A>C polymorphism.

Results

indicate that the MOTS-c gene (m.1382A>C) polymorphism shows no significant association with PCOS, and serum MOTS-c levels are comparable between individuals with PCOS and healthy controls, suggesting that MOTS-c may have a minor involvement in the pathophysiology of PCOS.

Source:10.1016/j.cmet.2015.01.013
Mechanistic Research SummaryCurated from PubMed

This data is for laboratory research purposes only. Not for human or animal consumption.

What is MOTS-c?

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a mitochondria-derived peptide that regulates metabolic homeostasis, insulin sensitivity, and obesity-related phenotypes. This study investigates its serum levels and genetic polymorphisms in adolescents with polycystic ovary syndrome (PCOS) to determine its role in reproductive metabolic dysfunction.

Mechanism of Action

MOTS-c functions as a signaling molecule that enhances insulin sensitivity and reduces metabolic dysfunction through mitochondrial-nuclear crosstalk. The peptide modulates glucose homeostasis and adipose tissue metabolism via activation of intracellular signaling pathways. The m.1382A>C polymorphism in the MOTS-c gene has been previously associated with impaired peptide function and increased type 2 diabetes risk in male populations, suggesting genetic variants may alter metabolic protection.

Observed Laboratory Results

  • Serum MOTS-c levels were marginally elevated in PCOS adolescents (121 subjects) compared to healthy controls (125 subjects), though this difference did not achieve statistical significance (p = 0.059), indicating minimal differential expression.
  • Gene polymorphism analysis revealed that 100% of study participants possessed the wild-type A/A genotype for the m.1382A>C variant; no heterozygous or homozygous mutant alleles were detected in the adolescent population studied.
  • No significant correlations were identified between serum MOTS-c concentrations and anthropometric parameters (BMI, waist circumference) or metabolic markers (fasting glucose, insulin, HOMA-IR) within the PCOS cohort (all p > 0.05).

Clinical Interpretation

These findings suggest MOTS-c likely plays a minor pathophysiological role in adolescent PCOS, and the m.1382A>C polymorphism exhibits limited population prevalence in this demographic. The absence of genetic variants limits mechanistic investigation of polymorphism-dependent dysfunction.

Clinical Research Parameters
4 trials

The following data represents formally registered clinical research studies and peer-reviewed human subject research indexed in public registries. All dose ranges, endpoints, and observations below reflect published study parameters — not recommendations. For research reference only.

Registered Clinical Trials
ClinicalTrials.gov ↗
NCT04013568 ↗
COMPLETEDN/An=62

Exercise Post-Diagnosis of Breast Cancer

The investigators are doing this study to determine if there are body composition changes after a 12-week exercise program in breast cancer patients and determine what factors contribute to sustained physical activity after the 12-week exercise program intervention.

Study Interventions
Exercise
Primary Endpoints
Fat mass; Isometric peak torque
Study Period
2019-08-28 → 2026-03-06
NCT04027712 ↗
UNKNOWNN/An=120

Platelet Reactivity, B-amyloid, MOTS-c and Mortality of Type II Diabetics With CAD

Increased circulating b-amyloid and decreased Mitochondrial-derived peptide (MOTS-c), a peptide improving tissue insulin sensitivity, are reported in diabetes. The investigators plan to investigate the association of both biofactors with high on-clopidogrel platelet reactivity and cardiovascular mortality in type 2 diabetic patients with Coronary artery disease

Primary Endpoints
mots-c predicts cardiovascular mortality in diabetic with coronary artery disease; b amyloid predicts cardiovascular mortality in diabetic with coronary artery disease
Study Period
2014-01-01 → 2021-12-31
NCT03878706 ↗
RECRUITINGN/An=240

The Cardiovascular Effect of GLP-1 Agonist, SGLT2 Inhibitor and Their Combination

A. Four groups of patients with type 2 diabetes mellitus with high or very high cardiovascular risk or heart failure with preserved ejection fraction (HFpEF) will be studied before and at 6 and 12 months of treatment: * 60 patients treated with a combination of GLP1 analogue and SGLT2 inhibitor ± metformin * 60 patients treated with GLP-1 agonist as a second step after metformin * 60 patients tre

Primary Endpoints
Comparison of Global Longitudinal Strain (GLS) difference among treatment groups.
Study Period
2017-11-03 → 2027-06-30
NCT07505745 ↗
RECRUITINGPhase IIn=120

MOTS-c for Improving Insulin Sensitivity in Adults With Prediabetes and Overweight/Obesity

This Phase 2a study evaluates whether 12 weeks of treatment with investigational MOTS-c improves insulin sensitivity compared with placebo in adults with prediabetes and overweight/obesity. Participants are randomized 1:1 to MOTS-c or placebo, receive standardized lifestyle counseling, and are followed for safety through Week 16.

Study Interventions
MOTS-c (MDP), Placebo, Route Subcutaneous injection
Primary Endpoints
Change from baseline in OGTT-derived insulin sensitivity (Matsuda Index); Incidence of treatment-emergent adverse events (TEAEs)
Study Period
2026-02-02 → 2028-05-17
Research Compliance Notice

All data presented on this page is for laboratory research purposes only. MOTS-c is referenced here as a research reagent. This page does not constitute medical advice, clinical guidance, or endorsement of any compound for human or animal use. All referenced studies are available via PubMed (PMID: 41945630) and the DOI-linked journal publication. Researchers must consult applicable institutional and regulatory frameworks before conducting any protocols.

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