MOTS-c repairs myocardial damage by inhibiting the CCN1/ERK1/2/EGR1 pathway in diabetic rats.

Wang M, Wang G, Pang X, Ma J, Yuan J, Pan Y, Fu Y, Laher I, Li S

Frontiers in nutrition4 Jan 2023Cited by 21 (Europe PMC)

PMID36687680PMCIDPMC9846618DOI10.3389/fnut.2022.1060684PepBankPUB-36687680

Summary

Cardiac structure remodeling and dysfunction are common complications of diabetes, often leading to serious cardiovascular events. MOTS-c, a mitochondria-derived peptide, regulates metabolic homeostasis by accelerating glucose uptake and improving insulin sensitivity. Plasma levels of MOTS-c are decreased in patients with diabetes. MOTS-c can improve vascular endothelial function, making it a novel therapeutic target for the cardiovascular complications of diabetes. We investigated the effects of MOTS-c on cardiac structure and function and analyzed transcriptomic characteristics in diabetic rats. Our results indicate that treatment with MOTS-c for 8-week repaired myocardial mitochondrial damage and preserved cardiac systolic and diastolic function. Transcriptomic analysis revealed that MOTS-c altered 47 disease causing genes. Functional enrichment analysis indicated MOTS-c attenuated diabetic heart disease involved apoptosis, immunoregulation, angiogenesis and fatty acid metabolism. Moreover, MOTS-c reduced myocardial apoptosis by downregulating CCN1 genes and thereby inhibiting the activation of ERK1/2 and the expression of its downstream EGR1 gene. Our findings identify potential therapeutic targets for the treatment of T2D and diabetic cardiomyopathy.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

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

01AnimalAnimal study (in vivo)Efficacy outcome
In diabetic rats, 8 weeks of MOTS‑c treatment repaired myocardial mitochondrial damage.
In plain wordsIn diabetic rats, MOTS‑c treatment repaired damage to the energy units of heart cells.
Peptide
MOTS-c
Outcome
DecreaseMyocardial mitochondrial damage
Study
ratn: not reported in source
Diabetic rats
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated · 8 weeksAs given in this study (rat).
Source sentences
Summary
Our results indicate that treatment with MOTS-c for 8-week repaired myocardial mitochondrial damage and preserved cardiac systolic and diastolic function.
1 context sentence(design, population, supporting numbers)
Summary · context
We investigated the effects of MOTS-c on cardiac structure and function and analyzed transcriptomic characteristics in diabetic rats.
Show in the study text Report a problemFND-3668768001
02AnimalAnimal study (in vivo)Efficacy outcome
In diabetic rats, 8 weeks of MOTS‑c treatment preserved cardiac systolic and diastolic function.
In plain wordsIn diabetic rats, MOTS‑c treatment preserved heart pumping and filling function.
Peptide
MOTS-c
Outcome
IncreaseCardiac systolic and diastolic function
Study
ratn: not reported in source
Diabetic rats
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated · 8 weeksAs given in this study (rat).
Source sentences
Summary
Our results indicate that treatment with MOTS-c for 8-week repaired myocardial mitochondrial damage and preserved cardiac systolic and diastolic function.
1 context sentence(design, population, supporting numbers)
Summary · context
We investigated the effects of MOTS-c on cardiac structure and function and analyzed transcriptomic characteristics in diabetic rats.
Show in the study text Report a problemFND-3668768002
03AnimalAnimal study (in vivo)Mechanism
In diabetic rats, transcriptomic analysis showed that MOTS‑c altered 47 disease-causing genes.
In plain wordsIn diabetic rats, MOTS‑c changed the activity of 47 genes linked to disease.
Peptide
MOTS-c
Outcome
Not applicableNumber of disease-causing genes altered (transcriptome)
Study
ratn: not reported in source
Diabetic rats
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
Dose not stated · 8 weeksAs given in this study (rat).
Source sentences
Summary
Transcriptomic analysis revealed that MOTS-c altered 47 disease causing genes.
1 context sentence(design, population, supporting numbers)
Summary · context
We investigated the effects of MOTS-c on cardiac structure and function and analyzed transcriptomic characteristics in diabetic rats.
Show in the study text Report a problemFND-3668768003
04AnimalAnimal study (in vivo)Mechanism
In diabetic rats, functional enrichment analysis linked the MOTS‑c effect on diabetic heart disease to apoptosis, immunoregulation, angiogenesis and fatty acid metabolism.
In plain wordsIn diabetic rats, MOTS‑c effects on the heart were linked to cell death, immune control, blood vessel growth and fat metabolism pathways.
Peptide
MOTS-c
Outcome
Not applicableEnriched pathways in diabetic heart disease
Study
ratn: not reported in source
Diabetic rats
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
Dose not stated · 8 weeksAs given in this study (rat).
Source sentences
Summary
Functional enrichment analysis indicated MOTS-c attenuated diabetic heart disease involved apoptosis, immunoregulation, angiogenesis and fatty acid metabolism.
1 context sentence(design, population, supporting numbers)
Summary · context
We investigated the effects of MOTS-c on cardiac structure and function and analyzed transcriptomic characteristics in diabetic rats.
Show in the study text Report a problemFND-3668768004
05AnimalAnimal study (in vivo)Mechanism
In diabetic rats, MOTS‑c reduced myocardial apoptosis.
In plain wordsIn diabetic rats, MOTS‑c reduced the death of heart muscle cells.
Peptide
MOTS-c
Outcome
DecreaseMyocardial apoptosis
Study
ratn: not reported in source
Diabetic rats
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated · 8 weeksAs given in this study (rat).
Source sentences
Summary
MOTS-c reduced myocardial apoptosis by downregulating CCN1 genes
1 context sentence(design, population, supporting numbers)
Summary · context
We investigated the effects of MOTS-c on cardiac structure and function and analyzed transcriptomic characteristics in diabetic rats.
Show in the study text Report a problemFND-3668768005
06AnimalAnimal study (in vivo)Mechanism
In diabetic rats, MOTS‑c downregulated CCN1 genes in the heart.
In plain wordsIn diabetic rats, MOTS‑c lowered the activity of the CCN1 gene in the heart.
Peptide
MOTS-c
Outcome
DecreaseCCN1 gene expression
Study
ratn: not reported in source
Diabetic rats
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
Dose not stated · 8 weeksAs given in this study (rat).
Source sentences
Summary
downregulating CCN1 genes and thereby inhibiting the activation of ERK1/2 and the expression of its downstream EGR1 gene.
1 context sentence(design, population, supporting numbers)
Summary · context
We investigated the effects of MOTS-c on cardiac structure and function and analyzed transcriptomic characteristics in diabetic rats.
Show in the study text Report a problemFND-3668768006
07AnimalAnimal study (in vivo)Mechanism
In diabetic rats, MOTS‑c inhibited the activation of ERK1/2 in the heart.
In plain wordsIn diabetic rats, MOTS‑c reduced the activation of the ERK1/2 signal in the heart.
Peptide
MOTS-c
Outcome
DecreaseERK1/2 activation
Study
ratn: not reported in source
Diabetic rats
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
Dose not stated · 8 weeksAs given in this study (rat).
Source sentences
Summary
inhibiting the activation of ERK1/2 and the expression of its downstream EGR1 gene.
1 context sentence(design, population, supporting numbers)
Summary · context
We investigated the effects of MOTS-c on cardiac structure and function and analyzed transcriptomic characteristics in diabetic rats.
Show in the study text Report a problemFND-3668768007
08AnimalAnimal study (in vivo)Mechanism
In diabetic rats, MOTS‑c inhibited expression of the downstream EGR1 gene.
In plain wordsIn diabetic rats, MOTS‑c lowered the activity of the EGR1 gene in the heart.
Peptide
MOTS-c
Outcome
DecreaseEGR1 gene expression
Study
ratn: not reported in source
Diabetic rats
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
Dose not stated · 8 weeksAs given in this study (rat).
Source sentences
Summary
the expression of its downstream EGR1 gene.
1 context sentence(design, population, supporting numbers)
Summary · context
We investigated the effects of MOTS-c on cardiac structure and function and analyzed transcriptomic characteristics in diabetic rats.
Show in the study text Report a problemFND-3668768008

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.

Version 2Current
10 Oct 2026, 08:19 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

Subjects

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