Aldehyde Dehydrogenase-2 Attenuates Myocardial Remodeling and Contractile Dysfunction Induced by a High-Fat Diet

作者：Li, Chuanbao; Li, Xiaoxing^*; Chang, Ying; Zhao, Lang; Liu, Baoshan; Wei, Shujian; Xu, Feng; Zhang, Yun; Chen, Yuguo^*

来源：Cellular Physiology and Biochemistry, 2018, 48(5): 1843-1853.

DOI：10.1159/000492506

• Metabolic syndrome
• Myocardial remodeling
• Apoptosis
• ALDH2
• Mice

Background/Aims: Consumption of a high-fat (HF) diet exacerbates metabolic cardiomyopathy through lipotoxic mechanisms. In this study, we explored the role of aldehyde dehydrogenase-2 (ALDH2) in myocardial damage induced by a HF diet. Methods: Wild-type C57 BL/6J mice were fed a HF diet or control diet for 16 weeks. ALDH2 overexpression was achieved by injecting a lentiviral ALDH2 expression vector into the left ventricle. Results: Consumption of a HF diet induced metabolic syndrome and myocardial remodeling, and these deleterious effects were attenuated by ALDH2 overexpression. In addition, ALDH2 overexpression attenuated the cellular apoptosis and insulin resistance associated with a HF diet. Mechanistically, ALDH2 overexpression inhibited the expression of c-Jun N-terminal kinase (JNK)-1, activated protein 1 (AP-1), insulin receptor substrate 1 (IRS-1), 4-hydroxynonenal, caspase 3, transforming growth factor beta 1, and collagen I and III, and enhanced Akt phosphorylation. Conclusion: ALDH2 may effectively attenuate myocardial remodeling and contractile defects induced by a HF diet through the regulation of the JNK/AP-1 and IRS-1/Akt signaling pathways. Our study demonstrates that ALDH2 plays an essential role in protecting cardiac function from lipotoxic cardiomyopathy.

• 出版日期2018
• 单位山东大学