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Magnolia bioactive constituent 4-O-methylhonokiol prevents the impairment of cardiac insulin signaling and the cardiac pathogenesis in high-fat diet-induced obese mice.

Zhang Z, Chen J, Zhou S, Wang S, Cai X, Conklin DJ, Kim KS, Kim KH, Tan Y, Zheng Y, Kim YH, Cai L - Int. J. Biol. Sci. (2015)

Bottom Line: Mechanistically, MH treatment significantly reduced HFD-induced impairment of cardiac insulin signaling by preferentially augmenting Akt2 signaling.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.

View Article: PubMed Central - PubMed

Affiliation: 1. Department of Cardiology at the First Hospital of Jilin University, Changchun, 130021, China ; 2. The Chinese-American Research Institute for Diabetic Complications and the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325035, China ; 3. Kosair Children's Hospital Research Institute, Department of Pediatrics of University of Louisville, Louisville, KY 40202.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Effects of MH on HFD-induced BP change and cardiac hypertrophy in mice. Systolic BP was measured by non-invasive tail cuff Plethysmograph system (A). Cardiac wall thickness was measured by echocardiography including diastolic interventricular septum (IVS, B) and diastolic left ventricular posterior wall (LVPW, C). At the same time, the ejection fraction (EF, D) was calculated using Vevo770 software. Data are presented as means ± SD (n=5). a, p<0.05 vs. ND; b, p< 0.05 vs. HFD.
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Figure 2: Effects of MH on HFD-induced BP change and cardiac hypertrophy in mice. Systolic BP was measured by non-invasive tail cuff Plethysmograph system (A). Cardiac wall thickness was measured by echocardiography including diastolic interventricular septum (IVS, B) and diastolic left ventricular posterior wall (LVPW, C). At the same time, the ejection fraction (EF, D) was calculated using Vevo770 software. Data are presented as means ± SD (n=5). a, p<0.05 vs. ND; b, p< 0.05 vs. HFD.

Mentions: Although neither the ND nor HFD led to an obvious change in systolic BP (Fig. 2A), echocardiography examination indicated that HFD feeding induced cardiac hypertrophy as indicated by increased wall thickness including diastolic IVS and diastolic LVPW compared with those in ND-fed mice (Fig. 2B,C). MH and BL153 treatments significantly attenuated cardiac hypertrophy induced by HFD feeding (Fig. 2B,C). No change in overall myocardial systolic function was detected (as per EF; Fig. 2D) between ND- and HFD-fed mice. Treatment with MH and BL153 did not affect myocardial systolic function or systolic BP in ND- and HFD-fed mice (Fig. 2D).


Magnolia bioactive constituent 4-O-methylhonokiol prevents the impairment of cardiac insulin signaling and the cardiac pathogenesis in high-fat diet-induced obese mice.

Zhang Z, Chen J, Zhou S, Wang S, Cai X, Conklin DJ, Kim KS, Kim KH, Tan Y, Zheng Y, Kim YH, Cai L - Int. J. Biol. Sci. (2015)

Effects of MH on HFD-induced BP change and cardiac hypertrophy in mice. Systolic BP was measured by non-invasive tail cuff Plethysmograph system (A). Cardiac wall thickness was measured by echocardiography including diastolic interventricular septum (IVS, B) and diastolic left ventricular posterior wall (LVPW, C). At the same time, the ejection fraction (EF, D) was calculated using Vevo770 software. Data are presented as means ± SD (n=5). a, p<0.05 vs. ND; b, p< 0.05 vs. HFD.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4495406&req=5

Figure 2: Effects of MH on HFD-induced BP change and cardiac hypertrophy in mice. Systolic BP was measured by non-invasive tail cuff Plethysmograph system (A). Cardiac wall thickness was measured by echocardiography including diastolic interventricular septum (IVS, B) and diastolic left ventricular posterior wall (LVPW, C). At the same time, the ejection fraction (EF, D) was calculated using Vevo770 software. Data are presented as means ± SD (n=5). a, p<0.05 vs. ND; b, p< 0.05 vs. HFD.
Mentions: Although neither the ND nor HFD led to an obvious change in systolic BP (Fig. 2A), echocardiography examination indicated that HFD feeding induced cardiac hypertrophy as indicated by increased wall thickness including diastolic IVS and diastolic LVPW compared with those in ND-fed mice (Fig. 2B,C). MH and BL153 treatments significantly attenuated cardiac hypertrophy induced by HFD feeding (Fig. 2B,C). No change in overall myocardial systolic function was detected (as per EF; Fig. 2D) between ND- and HFD-fed mice. Treatment with MH and BL153 did not affect myocardial systolic function or systolic BP in ND- and HFD-fed mice (Fig. 2D).

Bottom Line: Mechanistically, MH treatment significantly reduced HFD-induced impairment of cardiac insulin signaling by preferentially augmenting Akt2 signaling.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.

View Article: PubMed Central - PubMed

Affiliation: 1. Department of Cardiology at the First Hospital of Jilin University, Changchun, 130021, China ; 2. The Chinese-American Research Institute for Diabetic Complications and the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325035, China ; 3. Kosair Children's Hospital Research Institute, Department of Pediatrics of University of Louisville, Louisville, KY 40202.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus