The protective effects of liraglutide in reducing lipid droplets accumulation and myocardial fibrosis in diabetic cardiomyopathy.

IF 6.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Chien-Yin Kuo, Sing-Hua Tsou, Edy Kornelius, Kuei-Chuan Chan, Kai-Wei Chang, Jung-Chi Li, Chien-Ning Huang, Chih-Li Lin
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引用次数: 0

Abstract

Background: Diabetes is a primary contributor to diabetic cardiomyopathy (DbCM), which is marked by metabolic imbalances such as elevated blood glucose and lipid levels, leading to significant structural and functional alterations in the myocardium. Elevated free fatty acids (FFAs) and hyperglycemia play critical roles in DbCM development, with FFAs inducing insulin resistance in cardiomyocytes and promoting lipid accumulation, resulting in oxidative stress and fibrosis. Current research suggests that glucagon-like peptide-1 (GLP-1) receptor agonists may effectively mitigate DbCM, although an effective treatment for this condition remains elusive, and the precise mechanisms of this protective effect are not fully understood.

Methods: In this study, we aimed to replicate diabetic glucolipotoxic conditions by treating differentiated H9c2 cells with high glucose and free fatty acids. Additionally, a diabetic cardiomyopathy model was induced in mice through high-fat diets. Both in vitro and in vivo models were used to investigate the protective effects of liraglutide on cardiomyocytes and elucidate its underlying molecular mechanisms.

Results: Our findings indicate that liraglutide significantly reduces lipid droplet (LD) formation and myocardial fibrosis, as evidenced by decreased expression of fibrosis markers, including TGF-β1 and collagen types I and III. Liraglutide also enhanced AMP-activated protein kinase (AMPK) activation, which improved mitochondrial function, increased antioxidant gene expression, enhanced insulin signaling, and reduced oxidative stress.

Conclusions: These results demonstrate the potential therapeutic role of liraglutide in managing diabetes-related cardiac complications, offering a comprehensive approach to improving cardiac outcomes in patients with diabetes.

利拉鲁肽减少糖尿病性心肌病脂滴积聚和心肌纤维化的保护作用。
背景:糖尿病是糖尿病性心肌病(DbCM)的主要诱因,其特征是代谢失衡,如血糖和脂质水平升高,导致心肌显著的结构和功能改变。游离脂肪酸(FFAs)升高和高血糖在DbCM的发展中起关键作用,游离脂肪酸诱导心肌细胞胰岛素抵抗,促进脂质积累,导致氧化应激和纤维化。目前的研究表明,胰高血糖素样肽-1 (GLP-1)受体激动剂可能有效缓解DbCM,尽管这种情况的有效治疗仍然难以捉摸,而且这种保护作用的确切机制尚未完全了解。方法:在本研究中,我们旨在通过高糖和游离脂肪酸处理分化的H9c2细胞来复制糖尿病糖脂中毒条件。此外,通过高脂饮食诱导小鼠糖尿病性心肌病模型。采用体外和体内模型研究利拉鲁肽对心肌细胞的保护作用,并阐明其潜在的分子机制。结果:我们的研究结果表明,利拉鲁肽显著减少脂滴(LD)的形成和心肌纤维化,这可以通过降低纤维化标志物TGF-β1和I型、III型胶原的表达来证明。利拉鲁肽还能增强amp活化蛋白激酶(AMPK)的激活,从而改善线粒体功能,增加抗氧化基因表达,增强胰岛素信号传导,减少氧化应激。结论:这些结果表明利拉鲁肽在治疗糖尿病相关心脏并发症方面具有潜在的治疗作用,为改善糖尿病患者的心脏预后提供了一种全面的方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cellular and Molecular Life Sciences
Cellular and Molecular Life Sciences 生物-生化与分子生物学
CiteScore
13.20
自引率
1.20%
发文量
546
审稿时长
1.0 months
期刊介绍: Journal Name: Cellular and Molecular Life Sciences (CMLS) Location: Basel, Switzerland Focus: Multidisciplinary journal Publishes research articles, reviews, multi-author reviews, and visions & reflections articles Coverage: Latest aspects of biological and biomedical research Areas include: Biochemistry and molecular biology Cell biology Molecular and cellular aspects of biomedicine Neuroscience Pharmacology Immunology Additional Features: Welcomes comments on any article published in CMLS Accepts suggestions for topics to be covered
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