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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 lipid accumulation in heart tissue. Cardiac lipid accumulation was detected by Oil Red O staining (20×, bar=50 µm) of cryosections (A). The area of Oil Red O staining was quantified as a fold difference from that in sections from ND-fed mice (B). Data are presented as means ± SD (n=10). a, p<0.05 vs. ND; b, p< 0.05 vs. HFD; c, p< 0.05 vs. HFD/BL153.
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Figure 7: Effects of MH on HFD-induced lipid accumulation in heart tissue. Cardiac lipid accumulation was detected by Oil Red O staining (20×, bar=50 µm) of cryosections (A). The area of Oil Red O staining was quantified as a fold difference from that in sections from ND-fed mice (B). Data are presented as means ± SD (n=10). a, p<0.05 vs. ND; b, p< 0.05 vs. HFD; c, p< 0.05 vs. HFD/BL153.

Mentions: Lipid accumulation in cardiomyocytes is a marker of lipotoxicity and a feature of HFD-induced obesity. Histological detection by Oil Red O staining revealed that both MH and BL153 treatment significantly inhibited HFD-induced lipid accumulation in the heart. A quantitative analysis further showed that the area of Oil Red O staining in hearts of HFD-fed mice was almost 15 times higher than that present in ND-fed mice. This effect of the HFD was significantly reduced with either MH or BL153 treatment, and MH treatment results in a dose-dependent decrease in lipid accumulation that was more effective than that observed with BL153 treatment (Fig. 7). No lipid accumulation was observed in the ND-fed groups.


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 lipid accumulation in heart tissue. Cardiac lipid accumulation was detected by Oil Red O staining (20×, bar=50 µm) of cryosections (A). The area of Oil Red O staining was quantified as a fold difference from that in sections from ND-fed mice (B). Data are presented as means ± SD (n=10). a, p<0.05 vs. ND; b, p< 0.05 vs. HFD; c, p< 0.05 vs. HFD/BL153.
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Related In: Results  -  Collection

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

Figure 7: Effects of MH on HFD-induced lipid accumulation in heart tissue. Cardiac lipid accumulation was detected by Oil Red O staining (20×, bar=50 µm) of cryosections (A). The area of Oil Red O staining was quantified as a fold difference from that in sections from ND-fed mice (B). Data are presented as means ± SD (n=10). a, p<0.05 vs. ND; b, p< 0.05 vs. HFD; c, p< 0.05 vs. HFD/BL153.
Mentions: Lipid accumulation in cardiomyocytes is a marker of lipotoxicity and a feature of HFD-induced obesity. Histological detection by Oil Red O staining revealed that both MH and BL153 treatment significantly inhibited HFD-induced lipid accumulation in the heart. A quantitative analysis further showed that the area of Oil Red O staining in hearts of HFD-fed mice was almost 15 times higher than that present in ND-fed mice. This effect of the HFD was significantly reduced with either MH or BL153 treatment, and MH treatment results in a dose-dependent decrease in lipid accumulation that was more effective than that observed with BL153 treatment (Fig. 7). No lipid accumulation was observed in the ND-fed groups.

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