PMID- 37957221
OWN - NLM
STAT- MEDLINE
DCOM- 20231115
LR  - 20231124
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 13
IP  - 1
DP  - 2023 Nov 13
TI  - The role of MOTS-c-mediated antioxidant defense in aerobic exercise alleviating 
      diabetic myocardial injury.
PG  - 19781
LID - 10.1038/s41598-023-47073-0 [doi]
LID - 19781
AB  - 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.
CI  - (c) 2023. The Author(s).
FAU - Tang, Mi
AU  - Tang M
AD  - School of Physical Education, Xihua University, Chengdu, 610039, China.
AD  - Institute of Sports Medicine and Health, Chengdu Sport University, Chengdu, 
      610041, China.
FAU - Su, Quansheng
AU  - Su Q
AD  - Institute of Sports Medicine and Health, Chengdu Sport University, Chengdu, 
      610041, China.
FAU - Duan, Yimei
AU  - Duan Y
AD  - Institute of Sports Medicine and Health, Chengdu Sport University, Chengdu, 
      610041, China.
FAU - Fu, Yu
AU  - Fu Y
AD  - Institute of Sports Medicine and Health, Chengdu Sport University, Chengdu, 
      610041, China.
FAU - Liang, Min
AU  - Liang M
AD  - Institute of Sports Medicine and Health, Chengdu Sport University, Chengdu, 
      610041, China.
FAU - Pan, Yanrong
AU  - Pan Y
AD  - Institute of Sports Medicine and Health, Chengdu Sport University, Chengdu, 
      610041, China.
FAU - Yuan, Jinghan
AU  - Yuan J
AD  - Institute of Sports Medicine and Health, Chengdu Sport University, Chengdu, 
      610041, China.
FAU - Wang, Manda
AU  - Wang M
AD  - Institute of Sports Medicine and Health, Chengdu Sport University, Chengdu, 
      610041, China.
FAU - Pang, Xiaoli
AU  - Pang X
AD  - Institute of Sports Medicine and Health, Chengdu Sport University, Chengdu, 
      610041, China.
FAU - Ma, Jiacheng
AU  - Ma J
AD  - Institute of Sports Medicine and Health, Chengdu Sport University, Chengdu, 
      610041, China.
FAU - Laher, Ismail
AU  - Laher I
AD  - Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, 
      University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
FAU - Li, Shunchang
AU  - Li S
AD  - Institute of Sports Medicine and Health, Chengdu Sport University, Chengdu, 
      610041, China. lishunchang@cdsu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231113
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Antioxidants)
RN  - 0 (Kelch-Like ECH-Associated Protein 1)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - 0 (NF-E2-Related Factor 2)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
SB  - IM
MH  - Rats
MH  - Animals
MH  - *Antioxidants/metabolism
MH  - Kelch-Like ECH-Associated Protein 1/metabolism
MH  - *Diabetes Mellitus, Type 2/therapy/metabolism
MH  - AMP-Activated Protein Kinases/metabolism
MH  - NF-E2-Related Factor 2/metabolism
MH  - Exercise
MH  - Superoxide Dismutase/metabolism
MH  - Oxidative Stress
PMC - PMC10643467
COIS- The authors declare no competing interests.
EDAT- 2023/11/14 00:42
MHDA- 2023/11/15 06:42
PMCR- 2023/11/13
CRDT- 2023/11/13 23:28
PHST- 2023/05/24 00:00 [received]
PHST- 2023/11/08 00:00 [accepted]
PHST- 2023/11/15 06:42 [medline]
PHST- 2023/11/14 00:42 [pubmed]
PHST- 2023/11/13 23:28 [entrez]
PHST- 2023/11/13 00:00 [pmc-release]
AID - 10.1038/s41598-023-47073-0 [pii]
AID - 47073 [pii]
AID - 10.1038/s41598-023-47073-0 [doi]
PST - epublish
SO  - Sci Rep. 2023 Nov 13;13(1):19781. doi: 10.1038/s41598-023-47073-0.