Open Access4‐O‐methylhonokiol protects against diabetic cardiomyopathy in type 2 diabetic mice by activation of AMPK‐mediated cardiac lipid metabolism improvement
Author(s) -
Zheng Zongyu,
Ma Tianjiao,
Guo Hua,
Kim Ki Soo,
Kim Kyoung Tae,
Bi Liqi,
Zhang Zhiguo,
Cai Lu
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14493
Subject(s) - diabetic cardiomyopathy , ampk , ejection fraction , medicine , endocrinology , type 2 diabetes , cardiac function curve , insulin resistance , heart failure , cardiac fibrosis , dilated cardiomyopathy , lipid metabolism , beta oxidation , fibrosis , cardiomyopathy , inflammation , diabetes mellitus , chemistry , metabolism , protein kinase a , biochemistry , kinase
Abstract Diabetic cardiomyopathy (DCM) is characterized by increased left ventricular mass and wall thickness, decreased systolic function, reduced ejection fraction (EF) and ultimately heart failure. The 4‐O‐methylhonokiol (MH) has been isolated mainly from the bark of the root and stem of Magnolia species. In this study, we aimed to elucidate whether MH can effectively prevent DCM in type 2 diabetic (T2D) mice and, if so, whether the protective response of MH is associated with its activation of AMPK‐mediated inhibition of lipid accumulation and inflammation. A total number of 40 mice were divided into four groups: Ctrl, Ctrl + MH, T2D, T2D + MH. Five mice from each group were sacrificed after 3‐month MH treatment. The remaining animals in each group were kept for additional 3 months without further MH treatment. In T2D mice, the typical DCM symptoms were induced as expected, reflected by decreased ejection fraction and lipotoxic effects inducing lipid accumulation, oxidative stress, inflammatory reactions, and final fibrosis. However, these typical DCM changes were significantly prevented by the MH treatment immediately or 3 months after the 3‐month MH treatment, suggesting MH‐induced cardiac protection from T2D had a memory effect. Mechanistically, MH cardiac protection from DCM may be associated with its lipid metabolism improvement by the activation of AMPK/CPT1‐mediated fatty acid oxidation. In addition, the MH treatment of DCM mice significantly improved their insulin resistance levels by activation of GSK‐3β. These results indicate that the treatment of T2D with MH effectively prevents DCM probably via AMPK‐dependent improvement of the lipid metabolism.