Int J Biol Sci 2015; 11(8):879-891. doi:10.7150/ijbs.12101
Magnolia Bioactive Constituent 4-O-Methylhonokiol Prevents the Impairment of Cardiac Insulin Signaling and the Cardiac Pathogenesis in High-Fat Diet-Induced Obese Mice
1. Department of Cardiology at the First Hospital of Jilin University, Changchun, 130021, China
In obesity, cardiac insulin resistance is a putative cause of cardiac hypertrophy and dysfunction. In our previous study, we observed that Magnolia extract BL153 attenuated high-fat-diet (HFD)-induced cardiac pathogenic changes. In this study, we further investigated the protective effects of the BL153 bioactive constituent, 4-O-methylhonokiol (MH), against HFD-induced cardiac pathogenesis and its possible mechanisms. C57BL/6J mice were fed a normal diet or a HFD with gavage administration of vehicle, BL153, or MH (low or high dose) daily for 24 weeks. Treatment with MH attenuated HFD-induced obesity, as evidenced by body weight gain, and cardiac pathogenesis, as assessed by the heart weight and echocardiography. Mechanistically, MH treatment significantly reduced HFD-induced impairment of cardiac insulin signaling by preferentially augmenting Akt2 signaling. MH also inhibited cardiac expression of the inflammatory factors tumor necrosis factor-α and plasminogen activator inhibitor-1 and increased the phosphorylation of nuclear factor erythroid-derived 2-like 2 (Nrf2) as well as the expression of a Nrf2 downstream target gene heme oxygenase-1. The increased Nrf2 signaling was associated with decreased oxidative stress and damage, as reflected by lowered malondialdehyde and 3-nitrotyrosine levels. Furthermore, MH reduced HFD-induced cardiac lipid accumulation along with lowering expression of cardiac fatty acid translocase/CD36 protein. These results suggest that MH, a bioactive constituent of Magnolia, prevents HFD-induced cardiac pathogenesis by attenuating the impairment of cardiac insulin signaling, perhaps via activation of Nrf2 and Akt2 signaling to attenuate CD36-mediated lipid accumulation and lipotoxicity.
Keywords: Nrf2, obesity, lipid accumulation, lipotoxicity, cardiac insulin signaling, 4-O-methylhonokiol
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How to cite this article:
Zhang Z, Chen J, Zhou S, Wang S, Cai X, Conklin DJ, Kim KS, Kim KH, Tan Y, Zheng Y, Kim YH, Cai L. Magnolia Bioactive Constituent 4-O-Methylhonokiol Prevents the Impairment of Cardiac Insulin Signaling and the Cardiac Pathogenesis in High-Fat Diet-Induced Obese Mice. Int J Biol Sci 2015; 11(8):879-891. doi:10.7150/ijbs.12101. Available from http://www.ijbs.com/v11p0879.htm