Pentamethylquercetin Attenuates Cardiac Remodeling via Activation of the Sestrins/Keap1/Nrf2 Pathway in MSG-Induced Obese Mice

• Published in: BioMed research international Vol. 2020; no. 2020; pp. 1 - 10
• Main Authors: Liang, Gaofeng, Wang, Min, Li, Zhi, Wu, Jianzhao, Zhang, Cai, He, Wei, Du, Jingxia, Feng, Shuying
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 2020; Hindawi; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Abnormalities; Age; Animals; Antioxidants; Antioxidants - metabolism; Biomedical research; Cardiomegaly - complications; Cardiomegaly - diagnostic imaging; Cardiomegaly - physiopathology; Cardiomegaly - prevention & control; Cardiomyopathy; Cell Nucleus - drug effects; Cell Nucleus - metabolism; Disorders; Echocardiography; Electrocardiography; Ethylenediaminetetraacetic acid; Female; Fibrosis; Gene expression; Glutamate; Heart; Insulin resistance; Kelch-Like ECH-Associated Protein 1 - metabolism; Laboratory animals; Male; Metabolic disorders; Metabolism; Mice; Mice, Obese; Monosodium glutamate; Morphology; Myocardium - pathology; NF-E2-Related Factor 2 - metabolism; Nuclear Proteins - metabolism; Nuclear transport; Obesity; Obesity - complications; Obesity - drug therapy; Organ Size - drug effects; Oxidative stress; Phenotypes; Polyclonal antibodies; Protein Transport - drug effects; Proteins; Proteolysis - drug effects; Quercetin - analogs & derivatives; Quercetin - pharmacology; Quercetin - therapeutic use; Signal transduction; Signal Transduction - drug effects; Signaling; Sodium Glutamate; Staining; Structure-function relationships; Translocation; Ventricular Remodeling - drug effects; Wall thickness; Western blotting; China
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2020/3243906

Objective. Obesity causes a variety of metabolic alterations that may contribute to abnormalities of the cardiac structure and function (obesity cardiomyopathy). In previous works, we have shown that pentamethylquercetin (PMQ) significantly improved metabolic disorders in obese mice and it inhibited pressure overload-induced cardiac remodeling in mice. However, its potential benefit in obesity cardiomyopathy remains unclear. The aim of this study was to investigate the effects of PMQ on cardiac remodeling in obese mice. Methods. We generated a monosodium glutamate-induced obese (MSG-IO) model in mice, which were treated with PMQ (5, 10, and 20 mg/kg) for 16 weeks consecutively. We examined the metabolic parameters and observed cardiac remodeling by performing cardiac echocardiography and Masson’s staining. The expression levels of molecules associated with the endogenous antioxidant system, including the sestrins/kelch-like ECH-associated protein 1 (Keap1)/Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway, were analyzed by western blotting and immunofluorescent staining. Results. We found that PMQ treatment significantly ameliorated obesity phenotypes and improved metabolic disorders in MSG-IO mice. PMQ decreased the heart wall thickness and attenuated cardiac fibrosis. Further study revealed that the protective effects of PMQ might be mediated by promoting Keap1 degradation and augmenting sestrins expression and Nrf2 nuclear translocation. Conclusion. Our findings indicated that PMQ ameliorated cardiac remodeling in obese mice by targeting the sestrins/Keap1/Nrf2 signaling pathway.