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.
Highlights
Obesity is becoming a serious health issue all over the world.[1]
In our pre‐ vious study, we found that MH reduced plasma TG and cholesterol levels and significantly improved high‐fat diet (HFD)‐induced insulin resistance in obese mice
Our results show the following important findings: (a) this is the first in vivo study on the role of MH in the prevention of type 2 diabetes (T2D)‐in‐ duced cardiac injury; (b) the administration of MH in T2D mice effec‐ tively attenuated cardiac lipid dysfunction, fibrosis, oxidative stress and inflammation
Summary
Obesity is becoming a serious health issue all over the world.[1]. In 2016, 39% of the adults of the global population (1.9 billion people aged 18 years and older) were overweighed (body‐mass index ≥25 kg/ m2). Cardiac intracellular FA oxidation was found to in‐ crease, whereas glucose oxidation was inhibited.[6] Evidence exists that the cardiac function in DCM can be ameliorated by reducing FA oxidation or increasing the glucose oxidation to regulate the car‐ diac energy metabolism.[7] There are two scenarios that can explain intramyocardial lipid accumulation: impaired FA oxidation and FA oversupply.[8] Carnitine palmitoyltransferase 1 (CPT1) level, a key en‐ zyme regulating the entry of FA into the mitochondria for oxidation, was decreased in T2D cardiomyopathy, which may contribute to mi‐ tochondrial FA oxidation impairment. If a pre‐ ventive effect was established, our purpose was to find whether this prophylactic effect of MH was associated with AMPK‐me‐ diated abnormal lipid metabolism and inflammation‐inhibiting activation
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