Department of Cardiovascular Surgery, Fourth Hospital of Harbin Medical Harbin, Heilongjiang, 150001, China China.
Department of Histology and Embryology, Mudanjiang Medical University, Mudanjiang Province, Heilongjiang, China.
Bioengineered. 2022 Jun;13(6):14670-14681. doi: 10.1080/21655979.2022.2066748.
Nesfatin-1 is a novel anorexigenic peptide that possesses antihyperglycemic and cardiovascular effects. We hypothesized that nesfatin-1 has a beneficial protective effect against diabetic cardiomyopathy (DC). We investigated the therapeutic effect of nesfatin-1 on diabetes-associated cardiac dysfunction in the high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mouse model. We found that the cardiac nesfatin-1 level was lower in diabetic mice than in normal mice. Nesfatin-1 treatment (180 mg/kg/day for two weeks) improved insulin sensitivity and mitigated diabetic dyslipidemia. Nesfatin-1 ameliorated the diabetes-related myocardial hypertrophy and heart dysfunction, as revealed by the reduced hypertrophy index, heart rate, mean arterial pressure (MAP), creatine kinase (CK)-MB, and aspartate aminotransferase (AST) levels. Nesfatin-1 exerted antioxidant and anti-inflammatory activity in diabetic mice, as shown by decreased reactive oxygen species (ROS), oxidative lipid product malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) and glutathione (GSH), decreased cardiac and plasma interleukin-1 β (IL-1β) and tumor necrosis factor-α (TNF-α) levels. Mechanistically, we found that nesfatin-1 inhibited the cardiac p38-MAPK pathway activation and subsequent glucagon-like peptide-1 (GLP-1) level. Collectively, our data shows nesfatin-1 exerted protective effects against diabetic cardiomyopathy. Our study suggests that nesfatin-1 therapy has therapeutic implications against diabetic cardiomyopathy.
内脂素-1 是一种新型的厌食肽，具有降血糖和心血管作用。我们假设内脂素-1 对糖尿病心肌病（DC）具有有益的保护作用。我们研究了内脂素-1 对高脂肪饮食（HFD）/链脲佐菌素（STZ）诱导的糖尿病小鼠模型中与糖尿病相关的心脏功能障碍的治疗作用。我们发现糖尿病小鼠心脏中的内脂素-1 水平低于正常小鼠。内脂素-1 治疗（180mg/kg/天，持续两周）可改善胰岛素敏感性并减轻糖尿病血脂异常。内脂素-1 改善了与糖尿病相关的心肌肥大和心功能障碍，表现为肥大指数、心率、平均动脉压（MAP）、肌酸激酶（CK）-MB 和天冬氨酸氨基转移酶（AST）水平降低。内脂素-1 在糖尿病小鼠中发挥抗氧化和抗炎作用，表现为活性氧（ROS）、氧化脂质产物丙二醛（MDA）水平降低，超氧化物歧化酶（SOD）和谷胱甘肽（GSH）水平升高，心脏和血浆白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）水平降低。从机制上讲，我们发现内脂素-1 抑制了心脏 p38-MAPK 通路的激活及其随后的胰高血糖素样肽-1（GLP-1）水平。总之，我们的数据表明内脂素-1 对糖尿病心肌病具有保护作用。我们的研究表明，内脂素-1 治疗对糖尿病心肌病具有治疗意义。
