The role of MOTS-c-mediated antioxidant defense in aerobic exercise alleviating diabetic myocardial injury.

Tang M, Su Q, Duan Y, Fu Y, Liang M, Pan Y, Yuan J, Wang M, Pang X, Ma J, Laher I, Li S

Scientific reports13 Nov 2023Cited by 26 (Europe PMC)

PMID37957221PMCIDPMC10643467DOI10.1038/s41598-023-47073-0PepBankPUB-37957221

Summary

Myocardial remodeling and dysfunction are commonly observed in type 2 diabetes mellitus (T2DM). Aerobic exercise can partly alleviate diabetes-induced myocardial dysfunction through its antioxidant actions. MOTS-c is a potential exercise mimic. This study aimed to investigate the effects of MOTS-c on improving diabetic heart function and its mechanism and to identify whether MOTS-c improved antioxidant defenses due to aerobic exercise. Herein, we established a rat model of T2DM induced by high-fat diet combined with a low-dose streptozotocin injection. Interventions were performed using intraperitoneal injections of MOTS-c (i.p. 0.5 mg/kg/day, 7 days/week) or aerobic exercise training (treadmill, 20 m/min, 60 min/day, 5 days/week) for 8 weeks. Myocardial ultrastructure was assessed using transmission electron microscopy (TEM), myocardial lipid peroxidation levels (MDA), superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) levels were assessed using colorimetric methods, and molecular analyses including MOTS-c, Kelch-like ECH-associated protein 1 (Keap1), Nuclear factor E2-related factor 2 (Nrf2), adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)and phospho-AMPK (p-AMPK) were examined using Western blot. The results showed that MOTS-c, with or without exercise, reduced myocardial ultrastructural damage and improved glucolipid metabolism and cardiac function in T2DM. Furthermore, MOTS-c increased antioxidant markers such as SOD, CAT, and the protein expression of myocardial MOTS-c, Keap1, Nrf2, and p-AMPK. MOTS-c with exercise treatment reduced myocardial MDA and increased p-AMPK significantly comparing to only exercise or MOTS-c alone. Our findings suggest that MOTS-c may be a helpful supplement for overcoming exercise insufficiency and improving myocardial structure and function in diabetes.

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

Results from this study11

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

01AnimalAnimal study (in vivo)Efficacy outcome
In rats with type 2 diabetes, MOTS‑c, with or without exercise, reduced myocardial ultrastructural damage.
In plain wordsIn diabetic rats, MOTS‑c, with or without exercise, reduced damage to the fine structure of the heart muscle.
Peptide
MOTS-c
Outcome
DecreaseMyocardial ultrastructural damage
Study
ratn: not reported in source
Type 2 diabetes (high-fat diet plus low-dose streptozotocin)
Outcome group
Heart function · Cardiovascular
Studied dose
0.5 mg/kg/day · intraperitoneal · 8 weeksAs given in this study (rat).
Source sentences
Summary
MOTS-c, with or without exercise, reduced myocardial ultrastructural damage
2 context sentences(design, population, supporting numbers)
Summary · context
Herein, we established a rat model of T2DM induced by high-fat diet combined with a low-dose streptozotocin injection.
Summary · context
Interventions were performed using intraperitoneal injections of MOTS-c (i.p. 0.5 mg/kg/day, 7 days/week) or aerobic exercise training (treadmill, 20 m/min, 60 min/day, 5 days/week) for 8 weeks.
Show in the study text Report a problemFND-3795722101
02AnimalAnimal study (in vivo)Efficacy outcome
In rats with type 2 diabetes, MOTS‑c, with or without exercise, improved glucolipid metabolism.
In plain wordsIn diabetic rats, MOTS‑c, with or without exercise, improved sugar and fat metabolism.
Peptide
MOTS-c
Outcome
Direction not reportedGlucolipid metabolism
Study
ratn: not reported in source
Type 2 diabetes (high-fat diet plus low-dose streptozotocin)
Outcome group
Glycemic control · Metabolic and weight
Studied dose
0.5 mg/kg/day · intraperitoneal · 8 weeksAs given in this study (rat).
Source sentences
Summary
MOTS-c, with or without exercise, reduced myocardial ultrastructural damage and improved glucolipid metabolism
2 context sentences(design, population, supporting numbers)
Summary · context
Herein, we established a rat model of T2DM induced by high-fat diet combined with a low-dose streptozotocin injection.
Summary · context
Interventions were performed using intraperitoneal injections of MOTS-c (i.p. 0.5 mg/kg/day, 7 days/week) or aerobic exercise training (treadmill, 20 m/min, 60 min/day, 5 days/week) for 8 weeks.
Show in the study text Report a problemFND-3795722102
03AnimalAnimal study (in vivo)Efficacy outcome
In rats with type 2 diabetes, MOTS‑c, with or without exercise, improved cardiac function.
In plain wordsIn diabetic rats, MOTS‑c, with or without exercise, improved heart function.
Peptide
MOTS-c
Outcome
Direction not reportedCardiac function
Study
ratn: not reported in source
Type 2 diabetes (high-fat diet plus low-dose streptozotocin)
Outcome group
Heart function · Cardiovascular
Studied dose
0.5 mg/kg/day · intraperitoneal · 8 weeksAs given in this study (rat).
Source sentences
Summary
MOTS-c, with or without exercise, reduced myocardial ultrastructural damage and improved glucolipid metabolism and cardiac function in T2DM
2 context sentences(design, population, supporting numbers)
Summary · context
Herein, we established a rat model of T2DM induced by high-fat diet combined with a low-dose streptozotocin injection.
Summary · context
Interventions were performed using intraperitoneal injections of MOTS-c (i.p. 0.5 mg/kg/day, 7 days/week) or aerobic exercise training (treadmill, 20 m/min, 60 min/day, 5 days/week) for 8 weeks.
Show in the study text Report a problemFND-3795722103
04AnimalAnimal study (in vivo)Efficacy outcome
In rats with type 2 diabetes, MOTS‑c increased the antioxidant marker SOD in the myocardium.
In plain wordsIn diabetic rats, MOTS‑c raised the antioxidant marker SOD in heart tissue.
Peptide
MOTS-c
Outcome
IncreaseMyocardial SOD
Study
ratn: not reported in source
Type 2 diabetes (high-fat diet plus low-dose streptozotocin)
Outcome group
Oxidative stress · Cardiovascular
Studied dose
0.5 mg/kg/day · intraperitoneal · 8 weeksAs given in this study (rat).
Source sentences
Summary
MOTS-c increased antioxidant markers such as SOD, CAT, and the protein expression of myocardial MOTS-c, Keap1, Nrf2, and p-AMPK.
2 context sentences(design, population, supporting numbers)
Summary · context
Herein, we established a rat model of T2DM induced by high-fat diet combined with a low-dose streptozotocin injection.
Summary · context
Interventions were performed using intraperitoneal injections of MOTS-c (i.p. 0.5 mg/kg/day, 7 days/week) or aerobic exercise training (treadmill, 20 m/min, 60 min/day, 5 days/week) for 8 weeks.
Show in the study text Report a problemFND-3795722104
05AnimalAnimal study (in vivo)Efficacy outcome
In rats with type 2 diabetes, MOTS‑c increased the antioxidant marker CAT in the myocardium.
In plain wordsIn diabetic rats, MOTS‑c raised the antioxidant marker CAT in heart tissue.
Peptide
MOTS-c
Outcome
IncreaseMyocardial CAT
Study
ratn: not reported in source
Type 2 diabetes (high-fat diet plus low-dose streptozotocin)
Outcome group
Oxidative stress · Cardiovascular
Studied dose
0.5 mg/kg/day · intraperitoneal · 8 weeksAs given in this study (rat).
Source sentences
Summary
MOTS-c increased antioxidant markers such as SOD, CAT, and the protein expression of myocardial MOTS-c, Keap1, Nrf2, and p-AMPK.
2 context sentences(design, population, supporting numbers)
Summary · context
Herein, we established a rat model of T2DM induced by high-fat diet combined with a low-dose streptozotocin injection.
Summary · context
Interventions were performed using intraperitoneal injections of MOTS-c (i.p. 0.5 mg/kg/day, 7 days/week) or aerobic exercise training (treadmill, 20 m/min, 60 min/day, 5 days/week) for 8 weeks.
Show in the study text Report a problemFND-3795722105
06AnimalAnimal study (in vivo)Mechanism
In rats with type 2 diabetes, MOTS‑c treatment increased the protein expression of MOTS‑c in the myocardium.
In plain wordsIn diabetic rats, MOTS‑c treatment raised MOTS‑c protein in heart tissue.
Peptide
MOTS-c
Outcome
IncreaseMyocardial MOTS-c protein expression
Study
ratn: not reported in source
Type 2 diabetes (high-fat diet plus low-dose streptozotocin)
Outcome group
Oxidative stress · Cardiovascular
Studied dose
0.5 mg/kg/day · intraperitoneal · 8 weeksAs given in this study (rat).
Source sentences
Summary
the protein expression of myocardial MOTS-c, Keap1, Nrf2, and p-AMPK.
2 context sentences(design, population, supporting numbers)
Summary · context
Herein, we established a rat model of T2DM induced by high-fat diet combined with a low-dose streptozotocin injection.
Summary · context
Interventions were performed using intraperitoneal injections of MOTS-c (i.p. 0.5 mg/kg/day, 7 days/week) or aerobic exercise training (treadmill, 20 m/min, 60 min/day, 5 days/week) for 8 weeks.
Show in the study text Report a problemFND-3795722106
07AnimalAnimal study (in vivo)Mechanism
In rats with type 2 diabetes, MOTS‑c increased Keap1 protein expression in the myocardium.
In plain wordsIn diabetic rats, MOTS‑c raised Keap1 protein in heart tissue.
Peptide
MOTS-c
Outcome
IncreaseMyocardial Keap1 protein expression
Study
ratn: not reported in source
Type 2 diabetes (high-fat diet plus low-dose streptozotocin)
Outcome group
Oxidative stress · Cardiovascular
Studied dose
0.5 mg/kg/day · intraperitoneal · 8 weeksAs given in this study (rat).
Source sentences
Summary
the protein expression of myocardial MOTS-c, Keap1, Nrf2, and p-AMPK.
2 context sentences(design, population, supporting numbers)
Summary · context
Herein, we established a rat model of T2DM induced by high-fat diet combined with a low-dose streptozotocin injection.
Summary · context
Interventions were performed using intraperitoneal injections of MOTS-c (i.p. 0.5 mg/kg/day, 7 days/week) or aerobic exercise training (treadmill, 20 m/min, 60 min/day, 5 days/week) for 8 weeks.
Show in the study text Report a problemFND-3795722107
08AnimalAnimal study (in vivo)Mechanism
In rats with type 2 diabetes, MOTS‑c increased Nrf2 protein expression in the myocardium.
In plain wordsIn diabetic rats, MOTS‑c raised Nrf2 protein in heart tissue.
Peptide
MOTS-c
Outcome
IncreaseMyocardial Nrf2 protein expression
Study
ratn: not reported in source
Type 2 diabetes (high-fat diet plus low-dose streptozotocin)
Outcome group
Oxidative stress · Cardiovascular
Studied dose
0.5 mg/kg/day · intraperitoneal · 8 weeksAs given in this study (rat).
Source sentences
Summary
the protein expression of myocardial MOTS-c, Keap1, Nrf2, and p-AMPK.
2 context sentences(design, population, supporting numbers)
Summary · context
Herein, we established a rat model of T2DM induced by high-fat diet combined with a low-dose streptozotocin injection.
Summary · context
Interventions were performed using intraperitoneal injections of MOTS-c (i.p. 0.5 mg/kg/day, 7 days/week) or aerobic exercise training (treadmill, 20 m/min, 60 min/day, 5 days/week) for 8 weeks.
Show in the study text Report a problemFND-3795722108
09AnimalAnimal study (in vivo)Mechanism
In rats with type 2 diabetes, MOTS‑c increased p-AMPK protein expression in the myocardium.
In plain wordsIn diabetic rats, MOTS‑c raised p-AMPK protein in heart tissue.
Peptide
MOTS-c
Outcome
IncreaseMyocardial p-AMPK protein expression
Study
ratn: not reported in source
Type 2 diabetes (high-fat diet plus low-dose streptozotocin)
Outcome group
Oxidative stress · Cardiovascular
Studied dose
0.5 mg/kg/day · intraperitoneal · 8 weeksAs given in this study (rat).
Source sentences
Summary
the protein expression of myocardial MOTS-c, Keap1, Nrf2, and p-AMPK.
2 context sentences(design, population, supporting numbers)
Summary · context
Herein, we established a rat model of T2DM induced by high-fat diet combined with a low-dose streptozotocin injection.
Summary · context
Interventions were performed using intraperitoneal injections of MOTS-c (i.p. 0.5 mg/kg/day, 7 days/week) or aerobic exercise training (treadmill, 20 m/min, 60 min/day, 5 days/week) for 8 weeks.
Show in the study text Report a problemFND-3795722109
10AnimalAnimal study (in vivo)Efficacy outcome
In rats with type 2 diabetes, MOTS‑c with exercise reduced myocardial MDA more than exercise alone or MOTS‑c alone.
In plain wordsIn diabetic rats, MOTS‑c plus exercise lowered the heart oxidative damage marker MDA more than exercise alone or MOTS‑c alone.
Peptide
MOTS-c
Outcome
DecreaseMyocardial MDA with MOTS-c plus exercise
Study
ratn: not reported in source
Type 2 diabetes (high-fat diet plus low-dose streptozotocin)
Comparator
Exercise alone or MOTS-c alone
Outcome group
Oxidative stress · Cardiovascular
Studied dose
0.5 mg/kg/day · intraperitoneal · 8 weeksAs given in this study (rat).
Source sentences
Summary
MOTS-c with exercise treatment reduced myocardial MDA and increased p-AMPK significantly comparing to only exercise or MOTS-c alone.
2 context sentences(design, population, supporting numbers)
Summary · context
Herein, we established a rat model of T2DM induced by high-fat diet combined with a low-dose streptozotocin injection.
Summary · context
Interventions were performed using intraperitoneal injections of MOTS-c (i.p. 0.5 mg/kg/day, 7 days/week) or aerobic exercise training (treadmill, 20 m/min, 60 min/day, 5 days/week) for 8 weeks.
Show in the study text Report a problemFND-3795722110
11AnimalAnimal study (in vivo)Mechanism
In rats with type 2 diabetes, MOTS‑c with exercise increased p-AMPK significantly more than exercise alone or MOTS‑c alone.
In plain wordsIn diabetic rats, MOTS‑c plus exercise raised p-AMPK more than exercise alone or MOTS‑c alone.
Peptide
MOTS-c
Outcome
IncreaseMyocardial p-AMPK with MOTS-c plus exercise
Study
ratn: not reported in source
Type 2 diabetes (high-fat diet plus low-dose streptozotocin)
Comparator
Exercise alone or MOTS-c alone
Outcome group
Oxidative stress · Cardiovascular
Studied dose
0.5 mg/kg/day · intraperitoneal · 8 weeksAs given in this study (rat).
Source sentences
Summary
MOTS-c with exercise treatment reduced myocardial MDA and increased p-AMPK significantly comparing to only exercise or MOTS-c alone.
2 context sentences(design, population, supporting numbers)
Summary · context
Herein, we established a rat model of T2DM induced by high-fat diet combined with a low-dose streptozotocin injection.
Summary · context
Interventions were performed using intraperitoneal injections of MOTS-c (i.p. 0.5 mg/kg/day, 7 days/week) or aerobic exercise training (treadmill, 20 m/min, 60 min/day, 5 days/week) for 8 weeks.
Show in the study text Report a problemFND-3795722111

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
9 Oct 2026, 18:17 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

MeSH terms

PepBank is a research reference. Talk to a doctor before you use any peptide.