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Study · Animal study (in vivo) · mouse · 2021

8 results

A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c.

Zempo H, Kim SJ, Fuku N, Nishida Y, Higaki Y, Wan J, Yen K, Miller B, Vicinanza R, Miyamoto-Mikami E, Kumagai H, Naito H and 17 more

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Xiao J, Mehta HH, Lee C, Hara M, Patel YM, Setiawan VW, Moore TM, Hevener AL, Sutoh Y, Shimizu A, Kojima K, Kinoshita K, Arai Y, Hirose N, Maeda S, Tanaka K, Cohen P

Aging19 Jan 2021Cited by 49 (Europe PMC)

PMID33468709 (opens in a new tab)PMCIDPMC7880332 (opens in a new tab)DOI10.18632/aging.202529 (opens in a new tab)PepBankPUB-33468709
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Summary

Type 2 Diabetes (T2D) is an emerging public health problem in Asia. Although ethnic specific mtDNA polymorphisms have been shown to contribute to T2D risk, the functional effects of the mtDNA polymorphisms and the therapeutic potential of mitochondrial-derived peptides at the mtDNA polymorphisms are underexplored. Here, we showed an Asian-specific mitochondrial DNA variation m.1382A>C (rs111033358) leads to a K14Q amino acid replacement in MOTS-c, an insulin sensitizing mitochondrial-derived peptide. Meta-analysis of three cohorts (n = 27,527, J-MICC, MEC, and TMM) show that males but not females with the C-allele exhibit a higher prevalence of T2D. In J-MICC, only males with the C-allele in the lowest tertile of physical activity increased their prevalence of T2D, demonstrating a kinesio-genomic interaction. High-fat fed, male mice injected with MOTS-c showed reduced weight and improved glucose tolerance, but not K14Q-MOTS-c treated mice. Like the human data, female mice were unaffected. Mechanistically, K14Q-MOTS-c leads to diminished insulin-sensitization in vitro. Thus, the m.1382A>C polymorphism is associated with susceptibility to T2D in men, possibly interacting with exercise, and contributing to the risk of T2D in sedentary males by reducing the activity of MOTS-c.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

3 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In high-fat fed male mice, injected MOTS‑c reduced body weight, whereas K14Q-MOTS‑c did not.

    In plain wordsIn male mice on a high-fat diet, MOTS‑c injections lowered weight; the K14Q variant did not.

    Peptide
    MOTS-c
    Outcome
    DecreaseBody weight in high-fat fed male mice
    Study

    mousen: not reported in source

    High-fat fed male mice
    Comparator
    K14Q-MOTS-c
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    High-fat fed, male mice injected with MOTS-c showed reduced weight and improved glucose tolerance, but not K14Q-MOTS-c treated mice.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In high-fat fed male mice, injected MOTS‑c improved glucose tolerance, whereas K14Q-MOTS‑c did not.

    In plain wordsIn male mice on a high-fat diet, MOTS‑c injections improved glucose handling; the K14Q variant did not.

    Peptide
    MOTS-c
    Outcome
    IncreaseGlucose tolerance in high-fat fed male mice
    Study

    mousen: not reported in source

    High-fat fed male mice
    Comparator
    K14Q-MOTS-c
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    High-fat fed, male mice injected with MOTS-c showed reduced weight and improved glucose tolerance, but not K14Q-MOTS-c treated mice.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    Female mice were unaffected by MOTS‑c, in line with the human data.

    In plain wordsIn female mice, no effect was reported.

    Peptide
    MOTS-c
    Outcome
    No significant changeResponse to MOTS-c in female mice
    Study

    mousen: not reported in source

    Female mice
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Like the human data, female mice were unaffected.
    1 context sentence
    Summary · context
    High-fat fed, male mice injected with MOTS-c showed reduced weight and improved glucose tolerance, but not K14Q-MOTS-c treated mice.

Studies that did not test the peptide alone5

In this study, MOTS-c was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking MOTS-c.

  1. 04HumanNot a test of MOTS-c aloneObservational studyOther

    In a meta-analysis of three Asian cohorts, males with the m.1382A>C C-allele (K14Q in MOTS‑c) had a higher prevalence of type 2 diabetes; females did not.

    In plain wordsIn three cohorts, men with the C-allele variant had more type 2 diabetes than men without it; women did not.

    Peptide
    MOTS-c
    Outcome
    IncreaseT2D prevalence by m.1382A>C (K14Q) genotype in males
    Study

    n: not reported in source

    Comparator
    Non-carriers of the C-allele
    Outcome group
    Glycemic control · Metabolic and weight

    Source sentences

    Summary
    Meta-analysis of three cohorts (n = 27,527, J-MICC, MEC, and TMM) show that males but not females with the C-allele exhibit a higher prevalence of T2D.
    1 context sentence
    Summary · context
    Here, we showed an Asian-specific mitochondrial DNA variation m.1382A>C (rs111033358) leads to a K14Q amino acid replacement in MOTS-c, an insulin sensitizing mitochondrial-derived peptide.

    In this study, MOTS-c was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking MOTS-c.

  2. 05HumanNot a test of MOTS-c aloneObservational studyOther

    In the J-MICC cohort, only males with the C-allele in the lowest tertile of physical activity had an increased prevalence of type 2 diabetes.

    In plain wordsIn one cohort, only men with the C-allele variant who were least physically active had more type 2 diabetes.

    Peptide
    MOTS-c
    Outcome
    IncreaseT2D prevalence in C-allele males with low physical activity
    Study

    n: not reported in source

    Outcome group
    Glycemic control · Metabolic and weight

    Source sentences

    Summary
    In J-MICC, only males with the C-allele in the lowest tertile of physical activity increased their prevalence of T2D, demonstrating a kinesio-genomic interaction.

    In this study, MOTS-c was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking MOTS-c.

  3. 06AnimalNot a test of MOTS-c aloneAnimal study (in vivo)Efficacy outcome

    In high-fat fed male mice, the K14Q variant of MOTS‑c did not reduce body weight, unlike MOTS‑c.

    In plain wordsIn male mice on a high-fat diet, the K14Q variant did not lower weight, unlike normal MOTS‑c.

    Peptide
    MOTS-c
    Outcome
    No significant changeBody weight with K14Q-MOTS-c in high-fat fed male mice
    Study

    mousen: not reported in source

    High-fat fed male mice
    Comparator
    MOTS-c
    Outcome group
    Body weight · Metabolic and weight

    Source sentences

    Summary
    High-fat fed, male mice injected with MOTS-c showed reduced weight and improved glucose tolerance, but not K14Q-MOTS-c treated mice.

    In this study, MOTS-c was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking MOTS-c.

  4. 07AnimalNot a test of MOTS-c aloneAnimal study (in vivo)Efficacy outcome

    In high-fat fed male mice, the K14Q variant of MOTS‑c did not improve glucose tolerance, unlike MOTS‑c.

    In plain wordsIn male mice on a high-fat diet, the K14Q variant did not improve glucose handling, unlike normal MOTS‑c.

    Peptide
    MOTS-c
    Outcome
    No significant changeGlucose tolerance with K14Q-MOTS-c in high-fat fed male mice
    Study

    mousen: not reported in source

    High-fat fed male mice
    Comparator
    MOTS-c
    Outcome group
    Glycemic control · Metabolic and weight

    Source sentences

    Summary
    High-fat fed, male mice injected with MOTS-c showed reduced weight and improved glucose tolerance, but not K14Q-MOTS-c treated mice.

    In this study, MOTS-c was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking MOTS-c.

  5. 08LabNot a test of MOTS-c aloneIn vitro (cells)Mechanism

    In vitro, the K14Q variant of MOTS‑c led to diminished insulin sensitization.

    In plain wordsIn lab tests, the K14Q variant of MOTS‑c made cells less sensitive to insulin than expected.

    Peptide
    MOTS-c
    Outcome
    DecreaseInsulin sensitization by K14Q-MOTS-c in vitro
    Study

    n: not reported in source

    In vitro cell assay
    Outcome group
    Receptor activity and mechanism · Metabolic and weight

    Source sentences

    Summary
    Mechanistically, K14Q-MOTS-c leads to diminished insulin-sensitization in vitro.

    In this study, MOTS-c was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking MOTS-c.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    10 Oct 2026, 08:19 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 02:47 UTC

    First added · source update from Europe PMC

Subjects

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