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. 2015:2015:607531.
doi: 10.1155/2015/607531. Epub 2015 Dec 1.

Quercetin Alleviates High-Fat Diet-Induced Oxidized Low-Density Lipoprotein Accumulation in the Liver: Implication for Autophagy Regulation

Liang Liu  1 , Chao Gao  2 , Ping Yao  3 , Zhiyong Gong  1
Affiliations

Quercetin Alleviates High-Fat Diet-Induced Oxidized Low-Density Lipoprotein Accumulation in the Liver: Implication for Autophagy Regulation

Liang Liu et al. Biomed Res Int. 2015.

Abstract

A growing body of evidence has indicated that high-fat diet-induced nonalcoholic fatty liver disease is usually accompanied by oxidized low-density lipoprotein (ox-LDL) deposited in the liver. The current study aimed to investigate the effect of quercetin on high-fat diet-induced ox-LDL accumulation in the liver and to explore the potential underlying mechanisms. The results demonstrate that quercetin supplementation for 24 weeks significantly alleviated high-fat diet-induced liver damage and reduced hepatic cholesterol and ox-LDL level. Quercetin notably inhibited both mRNA and protein expression of CD36 (reduced by 53% and 71%, resp.) and MSR1 (reduced by 25% and 45%, resp.), which were upregulated by high-fat diet. The expression of LC3II was upregulated by 2.4 times whereas that of p62 and mTOR was downregulated by 57% and 63% by quercetin treatment. Therefore, the significantly improved autophagy lysosomal degradation capacity for ox-LDL may be implicated in the hepatoprotective effect of quercetin; scavenger receptors mediated ox-LDL uptake might also be involved.

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Figures

Figure 1
Figure 1
Effects of quercetin on hepatic histological changes and hepatic lipid content in mice fed with high-fat diet. Fixed liver tissue sections (three independent experiments) of mice (a) stained with H&E and (b) stained with anti-ox-LDL were observed under light microscope (magnification 40x); (c) hepatic lipids levels. ∗ P < 0.05 versus ND group, ∗∗ P < 0.01 versus ND group, and ## P < 0.01 versus HFD group (n = 10 for hepatic lipids levels).
Figure 2
Figure 2
Effects of quercetin on the expression of CD36 and MSR1 in the livers of mice fed with high-fat diet. Hepatic mRNA expression of CD36 (a) and MSR1 (b) was measured by RT-PCR. Protein levels of CD36 (c) and MSR1 (d) were determined with western blot analysis. Bar diagrams show densitometric data (c and d). Results expressed as mean ± SEM. ∗ P < 0.05 versus ND group, ∗∗ P < 0.01 versus ND group, # P < 0.05 versus HFD group, and ## P < 0.01 versus HFD group (n = 5 for RT-PCR in each group; n = 3 for others).
Figure 3
Figure 3
Quercetin supplementation increased the protein expression of LC3II and further downregulated the protein expression of mTOR and p62 induced by high-fat diet. Bar diagrams show densitometric data (a, b, and c). Results expressed as mean ± SEM. ∗ P < 0.05 versus ND group; # P < 0.05 versus HFD group (n = 4 for western blot analysis in each group).
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