The mitochondrial signaling peptide MOTS-c improves myocardial performance during exercise training in rats.
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ABSTRACT:
SUBMITTER: Yuan J
PROVIDER: S-EPMC8505603 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Myocardial infarction (MI) remains the leading cause of morbidity and mortality worldwide. Exercise training and pharmacological treatments are important strategies to minimize the deleterious effects of MI. However, little is known about the effects of resistance training combined with pyridostigmine bromide (PYR) treatment on cardiac and autonomic function, as well as on the inflammatory profile after MI. Thus, in the present study, male Wistar rats were randomly assigned into: control (Cont); sedentary infarcted (Inf); PYR - treated sedentary infarcted rats (Inf+P); infarcted rats undergoing resistance exercise training (Inf+RT); and infarcted rats undergoing PYR treatment plus resistance training (Inf+RT+P). After 12 weeks of resistance training (15-20 climbs per session, with a 1-min rest between each climb, at a low to moderate intensity, 5 days a week) and/or PYR treatment (0.14 mg/mL of drink water), hemodynamic function, autonomic modulation, and cytokine expressions were evaluated. We observed that 3 months of PYR treatment, either alone or in combination with exercise, can improve the deleterious effects of MI on left ventricle dimensions and function, baroreflex sensitivity, and autonomic parameters, as well as systemic and tissue inflammatory profile. Furthermore, additional benefits in a maximal load test and anti-inflammatory state of skeletal muscle were found when resistance training was combined with PYR treatment. Thus, our findings suggest that the combination of resistance training and PYR may be a good therapeutic strategy since they promote additional benefits on skeletal muscle anti-inflammatory profile after MI.
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Project description:Doxorubicin causes cardiotoxicity and exercise intolerance. Pre-conditioning exercise training seems to prevent doxorubicin-induced cardiac damage. However, the effectiveness of the cardioprotective effects of exercise training concomitantly with doxorubicin treatment remains largely unknown. To determine whether low-to-moderate intensity aerobic exercise training during doxorubicin treatment would prevent cardiotoxicity and exercise intolerance, we performed exercise training concomitantly with chronic doxorubicin treatment in mice. Ventricular structure and function were accessed by echocardiography, exercise tolerance by maximal exercise test, and cardiac biology by histological and molecular techniques. Doxorubicin-induced cardiotoxicity, evidenced by impaired ventricular function, cardiac atrophy, and fibrosis. Exercise training did not preserve left ventricular ejection fraction or reduced fibrosis. However, exercise training preserved myocardial circumferential strain alleviated cardiac atrophy and restored cardiomyocyte cross-sectional area. On the other hand, exercise training exacerbated doxorubicin-induced body wasting without affecting survival. Finally, exercise training blunted doxorubicin-induced exercise intolerance. Exercise training performed during doxorubicin-based chemotherapy can be a valuable approach to attenuate cardiotoxicity.
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Project description:Mitochondria are complex metabolic organelles with manifold pathophysiological implications in diabetes. Currently published mitochondrial-encoded peptides, which are expressed from the mitochondrial open reading frame of the 12S ribosomal RNA type-c (MOTS-c), 16S rRNA (humanin and short humanin like peptide 1-6 [SHLP1-6]), or small human mitochondrial open reading frame over serine tRNA (SHMOOSE) are associated with regulation of cellular metabolism and insulin action in age-related diseases, such as type 2 diabetes mellitus. This review focuses mainly on recent advances in MOTS-c research with regards to diabetes, including both type 1 and type 2. The emerging understanding of MOTS-c in diabetes may provide insight into the development of new therapies for diabetes and other age or senescence-related diseases.
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Project description:To test the hypothesis that early exercise training after myocardial infarction (MI) could preserve cardiac function, alleviate left ventricular (LV) remodeling and induce a protective effect on morphology, male Sprague-Dawley rats underwent coronary ligation or sham operation, and were assigned to 3 groups: Sham, sedentary MI (SedMI), and exercise MI (ExMI). We measured the changes in collagen volume fraction, matrix metalloproteinase (MMP) 1, tissue inhibitor matrix metalloproteinase 1 (TIMP-1), angiotensin II receptor type 1 (AT1), and angiotensin converting enzyme (ACE) at gene and protein levels after 8 weeks of exercise training. Cardiac functions were determined by echocardiographic and hemodynamic measurements. Early exercise training after MI had no effect on LV wall thinning. Cardiac function was significantly preserved in the ExMI group in comparison to the SedMI group. The collagen volume fraction in the ExMI group was significantly lower than in the SedMI group. Compared to the SedMI group, the ExMI group showed a markedly decrease at both the gene and protein levels in TIMP-1 (P<0.05). No significant differences were found in MMP-1 among the three groups. MMP-1/TIMP-1 ratio in the ExMI group was significantly higher than in the SedMI group. In addition, the expression of AT1 protein in the ExMI group was significantly lower than in the SedMI group. Furthermore, both ACE mRNA expression and ACE binding in the ExMI group are significantly decreased compared to the SedMI group. Our results suggest that early exercise training after MI reduces TIMP-1 expression, improves the balance between MMPs and TIMPs, and mitigates the expressions of ACE and AT1 receptor. These improvements, in turn, attenuate myocardial fibrosis and preserve post-MI cardiac function.
| S-EPMC2244592 | biostudies-literature
Project description:Probiotics exert multiple health benefits, including gastrointestinal health, immunoregulation, and metabolic disease improvement, by modulating microbiota to maintain eubiosis via the hypothalamic-pituitary-adrenal (HPA) and brain-gut-microbiome axes. Physiological fatigue, mental stress, and gastrointestinal discomfort under the demands of athletic performance as well as immunosuppression are common during endurance training and competition. Limited studies investigated the functional effects of probiotic supplementation on endurance training. Bifidobacterium longum subsp. Longum OLP-01 (OLP-01), isolated from an elite Olympic athlete, was combined with a six-week exercise training program with gradually increasing intensity. In this study, Institute of Cancer Research (ICR) mice were assigned to sedentary, exercise, OLP-01, or exercise + OLP-01 groups and administered probiotic and/or treadmill exercise training for six weeks to assess exercise performance, physiological adaption, and related metabolites. The exercise + OLP-01 group demonstrated higher performance in terms of endurance and grip strength, as well as improved fatigue-associated indexes (lactate, ammonia, creatine kinase (CK), lactate dehydrogenase (LDH), and glycogen content), compared with the other groups. OLP-01 supplementation significantly ameliorated inflammation and injury indexes (platelet/lymphocyte ratio (PLR), aminotransferase (AST), and CK) caused by prolonged endurance exercise test. Moreover, acetate, propionate, and butyrate levels were significantly higher in the exercise + OLP-01 group than in the sedentary and OLP-01 groups. Athletes often experience psychological and physiological stress caused by programed intensive exercise, competition, and off-site training, often leading to poor exercise performance and gastrointestinal issues. Functional OLP-01 probiotics are considered to be a nutritional strategy for improving physiological adaption, oxidative stress, inflammation, and energy balance to ensure high physical performance. Based on these results, probiotics combined with exercise training is a potential strategy for ensuring high physical performance of athletes, which should be further investigated through microbiota validation.
| S-EPMC7231274 | biostudies-literature
Project description:Kaempferol is a natural flavonoid with reported bioactivities, however its effects on exercise performance and muscle metabolism are unclear. This study investigated kaempferol for improving exercise performance and potential underlying mechanism in vivo and in vitro. In vitro, kaempferol promoted glucose uptake, protein synthesis and mitochondrial function along with decreasing oxidative stress in C2C12 myotubes. Moreover, the PI3K-AKT and MAPK signaling pathways were proved be activated with kaempferol by transcriptomic analysis.
2024-02-02 | GSE252790 | GEO
Project description:MOTS-c is a mitochondrial derived peptide with exercise mimetic activity that elicits beneficial effects on metabolism and exercise capacity. Furthermore, MOTS-c effects in humans are affected by race, potentially via ethnic-specific mtDNA variations. Women treated for breast cancer are at an increased risk for cardiovascular disease, diabetes and obesity, due to side effects of cancer-treatments. We conducted a secondary analysis of the effects of a 16-week aerobic and resistance exercise intervention on MOTS-c in Hispanic and Non-Hispanic White breast cancer survivors (BCS). BCS (Stage I-III) were randomized to exercise or standard care. The intervention promoted aerobic and resistance exercise for 16 weeks. MOTS-c was analyzed in fasting plasma using an in-house ELISA. Within and between group differences were assessed by paired t-test and repeated measures ANOVA. Pearson's correlation was computed to assess the association between MOTS-c and metabolic biomarkers at baseline and post-exercise. Twenty-five Hispanic-BCS and 24 non-Hispanic White BCS were included. Hispanic BCS were younger, of greater adiposity, had higher stage cancers, and had worse metabolic profiles at baseline compared to non-Hispanic White BCS (p < 0.001). Post-exercise, MOTS-c levels significantly increased when compared to baseline and the usual care group among non-Hispanic White BCS (p < 0.01) but not among Hispanic breast cancer survivors (p > 0.01). Post-exercise levels of MOTS-c among non-Hispanic White BCS were significantly associated with reductions in fat mass, body weight, HOMA-IR, CRP, and an increase in lean mass (p < 0.01). A 16-week aerobic and resistance intervention increased MOTS-c levels among non-Hispanic White BCS. Trial registration: This trial is registered on ClinicalTrials.gov: NCT01140282 as of June 9, 2010. https://clinicaltrials.gov/ct2/show/NCT01140282 .
| S-EPMC8376922 | biostudies-literature
Project description: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.
| S-EPMC7880332 | biostudies-literature
Project description:Mitochondria are ancient organelles that are thought to have emerged from once free-living α-proto-bacteria. As such, they still possess several bacterial-like qualities, including a semi-autonomous genetic system, complete with an independent genome and a unique genetic code. The bacterial-like circular mitochondrial DNA (mtDNA) has been described to encode 37 genes, including 22 tRNAs, 2 rRNAs, and 13 mRNAs. Two additional peptides reported to originate from the mtDNA, namely humanin (Hashimoto et al., 2001; Ikone et al., 2003; Guo et al., 2003) [1-3] and MOTS-c (mitochondrial ORF of the twelve S c) (Lee et al., 2015) [4], indicate a larger mitochondrial genetic repertoire (Shokolenko and Alexeyev, 2015) [5]. These mitochondrial-derived peptides (MDPs) have profound and distinct biological activities and provide a paradigm-shifting concept of active mitochondrial-encoded signals that act at the cellular and organismal level (i.e. mitochondrial hormone) (da Cunha et al., 2015; Quiros et al., 2016) [6,7]. Considering that mitochondria are the single most important metabolic organelle, it is not surprising that these MDPs have metabolic actions. MOTS-c has been shown to target the skeletal muscle and enhance glucose metabolism. As such, MOTS-c has implications in the regulation of obesity, diabetes, exercise, and longevity, representing an entirely novel mitochondrial signaling mechanism to regulate metabolism within and between cells.
| S-EPMC5116416 | biostudies-literature
Project description: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.
| S-EPMC10643467 | biostudies-literature