Wang Manda, Wang Gangqiang, Pang Xiaoli, Ma Jiacheng, Yuan Jinghan, Pan Yanrong, Fu Yu, Laher Ismail, Li Shunchang
Institute of Sports Medicine and Health, Chengdu Sport University, Chengdu, China.
Physical Education Section, Chengdu Textile College, Chengdu, China.
Front Nutr. 2023 Jan 4;9:1060684. doi: 10.3389/fnut.2022.1060684. eCollection 2022.
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.
心脏结构重塑和功能障碍是糖尿病常见的并发症，常导致严重的心血管事件。MOTS-c是一种线粒体衍生肽，通过加速葡萄糖摄取和提高胰岛素敏感性来调节代谢稳态。糖尿病患者血浆中MOTS-c水平降低。MOTS-c可改善血管内皮功能，使其成为糖尿病心血管并发症的新型治疗靶点。我们研究了MOTS-c对糖尿病大鼠心脏结构和功能的影响，并分析了转录组特征。我们的结果表明，用MOTS-c治疗8周可修复心肌线粒体损伤，并保留心脏的收缩和舒张功能。转录组分析显示，MOTS-c改变了47个致病基因。功能富集分析表明，MOTS-c减轻了涉及细胞凋亡、免疫调节、血管生成和脂肪酸代谢的糖尿病性心脏病。此外，MOTS-c通过下调CCN1基因来减少心肌细胞凋亡，从而抑制ERK1/2的激活及其下游EGR1基因的表达。我们的研究结果确定了治疗2型糖尿病和糖尿病性心肌病的潜在治疗靶点。
