Role of autophagy in a model of obesity: A long‑term high fat diet induces cardiac dysfunction

Che,Yan; Wang,Zhao‑Peng; Yuan,Yuan; Zhang,Ning; Jin,Ya‑Ge; Wan,Chun‑Xia; Tang,Qi‑Zhu

doi:10.3892/mmr.2018.9301

Role of autophagy in a model of obesity: A long‑term high fat diet induces cardiac dysfunction

Authors:
- Yan Che
- Zhao‑Peng Wang
- Yuan Yuan
- Ning Zhang
- Ya‑Ge Jin
- Chun‑Xia Wan
- Qi‑Zhu Tang
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Affiliations: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
Published online on: July 23, 2018 https://doi.org/10.3892/mmr.2018.9301
Pages: 3251-3261
Copyright: © Che et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Obesity may induce end‑organ damage through metabolic syndrome, and autophagy serves a vital role in the pathogenesis of metabolic syndrome. The purpose of the present study was to define the roles of autophagy and mitophagy in high fat diet (HFD)‑induced cardiomyopathy. Male, 8 week‑old C57BL/6 mice were fed either a HFD (60% kcal) or a diet of normal chow (NC; 10% kcal) for 42 weeks. Glucose tolerance tests were performed during the feeding regimes. Blood samples were collected for assaying serum triglyceride with the glycerol‑3‑phosphate oxidase phenol and aminophenazone (PAP) method and total cholesterol was tested with the cholesterol oxidase‑PAP method. Myocardial function was assessed using echocardiography and hemodynamic analyses. Western blot analysis was employed to evaluate endoplasmic reticulum stress (ERS), autophagy and mitochondrial function. Electron microscopy was used to assess the number of lipid droplets and the degree of autophagy within the myocardium. The body weight and adipose tissue weight of mice fed the HFD were increased compared with the NC mice. The serum levels of blood glucose, total cholesterol and triglyceride were significantly increased following 42 weeks of HFD feeding. The results of the glucose tolerance tests additionally demonstrated metabolic dysregulation in HFD mice. In addition, HFD mice exhibited hemodynamic and echocardiographic evidence of impaired diastolic and systolic function, including alterations in the cardiac output, end‑diastolic pressure, end‑diastolic volume and left ventricular relaxation time constant (tau) following HFD intake. Furthermore, a HFD resulted in increased ERS, and a downregulation of the autophagy and mitophagy level. The present study investigated cardiac function in obese HFD‑fed mice. These results aid the pursuit of novel therapeutic targets to combat obesity‑associated cardiomyopathy.

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