Artemisia iwayomogi extract attenuates high-fat diet-induced hypertriglyceridemia in mice: Potential involvement of the adiponectin-AMPK pathway and very low density lipoprotein assembly in the liver

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Abstract

This study aimed to examine the protective effect of Artemisia iwayomogi extract (AI) against hypertriglyceridemia induced by a high-fat diet (HFD) in mice and to uncover the underlying molecular mechanisms. C57BL/6N mice were fed chow, HFD, HFD + 0.1% AI, HFD + 0.25% AI, or HFD + 0.5% AI for 10 weeks. The addition of 0.25% and 0.5% AI resulted in dose-dependent improvements in the major parameters of hypertriglyceridemia, including plasma triglyceride, free fatty acids, apolipoprotein B, and lipoprotein lipase, with parallel reductions in body weight gain, hepatic lipid accumulation, and insulin resistance. These beneficial effects were accompanied by the activation of adiponectin-adenosine monophosphate-activated protein kinase (AMPK) mediated signaling cascades in the liver, which downregulated molecules involved in lipogenesis and concurrently upregulated molecules related to fatty acid oxidation. The downregulation of molecules involved in very low density lipoprotein assembly, which was associated with improved hepatic insulin signaling, also appeared to contribute to the AI-induced attenuation of hypertriglyceridemia.

Figures

  • Figure 1. Cont.
  • Figure 1. The contents of the individual bioactives identified in Artemisia iwayomogi extract (AI). (A) A representative high performance liquid chromatography (HPLC) chromatogram of the compound present in the extract is shown. The sample was run three times at 330 nm; (B) the molecular structures and concentrations (% w/w) of compounds identified in AI.
  • Figure 2. AI attenuates hypertriglyceridemia in high-fat diet (HFD)-fed mice. (A) Changes in body weight and food intake; (B) plasma levels of triglyceride, total apolipoprotein B, total cholesterol, very low density lipoprotein (VLDL) + LDL cholesterol, and high density lipoprotein (HDL) cholesterol; (C) plasma free fatty acid and lipoprotein lipase concentrations. Data are the mean ± standard error
  • Figure 3. AI alleviates hepatic steatosis in HFD-fed mice. (A) Liver weights and gross morphology; (B) representative images of H&E-stained sections of liver (scale bar = 100 µm) and scores for hepatic steatosis and inflammation; (C) hepatic levels of triglyceride, cholesterol, and free fatty acid; (D) plasma aminotransferase (ALT) and aspartate aminotransferase (AST) activities; Data are the mean ± SEM of n = 8. Statistical analysis was performed using one-way ANOVA and analyzed further by Duncan’s multiple range test. Different letters above the bars indicate significant differences among experimental groups (p < 0.05).
  • Figure 4. Cont.
  • Figure 5. AI improves the hepatic insulin signaling pathway in mice. (A) Fasting plasma levels of insulin and glucose and homeostasis model assessment of basal insulin resistance (HOMA-IR)) index; (B) oral glucose tolerance test (OGTT) and area under the curve (AUC); (C) densitometric quantification of the phosphorylation of IRS1, AKT, FOXO, and ApoB100 in the liver; (D) hepatic expression of genes involved in VLDL assembly; Statistical analysis was performed using one-way ANOVA and analyzed further by Duncan’s multiple range test. Different letters above the bars indicate significant differences among experimental groups (p < 0.05).
  • Figure 6. Schematic representation of mechanisms by which AI inhibits HFD-induced hypertriglyceridemia.

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CITATION STYLE

APA

Lee, J., Narayan, V. P., Hong, E. Y., Whang, W. K., & Park, T. (2017). Artemisia iwayomogi extract attenuates high-fat diet-induced hypertriglyceridemia in mice: Potential involvement of the adiponectin-AMPK pathway and very low density lipoprotein assembly in the liver. International Journal of Molecular Sciences, 18(8). https://doi.org/10.3390/ijms18081762

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