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

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Liang Liu ◽  
Chao Gao ◽  
Ping Yao ◽  
Zhiyong Gong

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.

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Aijun Sun ◽  
Xueting Jin ◽  
Jingjing Zhao ◽  
Keqiang Wang ◽  
Fang Xu ◽  
...  

Aims: Probucol, an agent characterized by lipid-lowering and anti-oxidant property, retards atherosclerosis effectively. Our study aimed to test the hypothesis that probucol might act its anti-athersclerotic role by suppressing maturation of human monocyte-derived dendritic cells (h-monDC). Furthermore, we also used a LDLR-/- mice model fed a high-fat diet to detect whether probucol also perform its anti-atherosclerotic effect on suppressing DCs maturation in vivo. Methods: H-monDCs were derived by incubating purified human monocytes with GM-CSF and IL-4. H-monDCs were pre-incubated with or without probucol and stimulated by oxidized low-density lipoprotein (ox-LDL) in the presence or absence of heme oxygenase (HO-1) siRNA. In vivo studies, streptozotocin (STZ) induced LDLR-/- mice were fed either a high-fat (HF) diet or added with 0.5% probucol for 4 months. Expression of h-monDC membrane molecules and mice splenic CD11c+DC membrane molecules were analyzed by FACS, cytokines were measured by ELISA and the STAT1/CIITA associated signaling pathway was determined by Western blotting. Mice aortic lesions were observed by En face staining and the expression of CD11c+DCs within atherosclerotic plaques were shown under confocal microscopy. Results: Ox-LDL promoted h-monDC maturation and TNF-a production; and up-regulated STAT1 701 phosphorylation by activating HO-1 in STAT1/CIITA signaling pathway. These effects were inhibited by probucol. Knocking down HO-1 with specific siRNA blocked these effects of probucol. In LDLR-/- mice fed a high-fat diet, probucol treatment significantly regressed aortic atherosclerotic lesions, suppressed splenic CD11c+DCs maturation and IL-12p70 production; and resulted in absence of CD11c+DCs within atherosclerotic lesions. Conclusions: Our study indicated that probucol effectively suppressed maturation of h-monDC induced by ox-LDL through HO-1 activation, and retarded atherosclerosis at least partly through inhibiting maturations of CD11c+DCs in LDLR-/- mice.


Author(s):  
Maria Donatella Semeraro ◽  
Gunter Almer ◽  
Melanie Kaiser ◽  
Sieglinde Zelzer ◽  
Andreas Meinitzer ◽  
...  

Abstract Purpose Regular exercise reduces obesity and the risk of cardiovascular disease. However, health-promoting benefits of physical activity are commonly associated with increased inflammation and oxidative stress. Here, we tested whether constant moderate exercise is able to prevent or attenuate the oxidative/nitrosative stress, inflammation, and serum lipids in lean and obese rats. Methods Four-month-old female Sprague Dawley rats received standard or a high-fat diet. Animals were subjected to a physical activity protocol, consisting of 30 min forced treadmill exercise for 5 consecutive days per week during 10 months. Baseline and sedentary (non-exercised) rats were used as controls. Lipids, oxidized low-density lipoprotein cholesterol, nitric oxide metabolites, and pro- and anti-inflammatory markers were measured in blood collected upon euthanasia. Results At variance to young baseline control rats, 14-month-old animals fed normal diet had increased plasma lipid levels, including total cholesterol and triglycerides, which were further elevated in rats that consumed a high-fat diet. While treadmill exercise did not lower the amount of serum lipids in standard diet group, forced physical activity reduced non-high-density lipoprotein cholesterol in response to high-fat diet feeding. Exercised rats fed standard diet or high-fat diet had lower abundancy of nitric oxide metabolites, which coincided with increased levels of oxidized low-density lipoprotein cholesterol. Accordingly, the amount of nitric oxide metabolites correlated inversely with oxidized low-density lipoprotein cholesterol and homo-arginine. Exercise significantly reduced inflammatory cytokines in high-fat diet fed rats only. Conclusion Our study suggests that regular exercise alters the equilibrium between oxidative and anti-oxidative compounds and reduces pro-inflammatory cytokines.


2020 ◽  
Vol 8 (2) ◽  
pp. 58-63
Author(s):  
Narjes Rezaei ◽  
Zahra Zaherijamil ◽  
Shirin Moradkhani ◽  
Massoud Saidijam ◽  
Iraj khodadadi ◽  
...  

Background: It is shown that kiwifruit elevates serum high-density lipoprotein cholesterol (HDL-C) levels and exhibits beneficial effects on human health due to its antioxidant potential. Objectives: This study aimed to investigate the impact of kiwifruit on the activity of the paraoxonase 1 (PON1) enzyme, as a main antioxidant enzyme in HDL functionality, in a high-fat diet (HFD). Methods: To this end, 42 male Syrian hamsters were divided into 6 groups including hamsters receiving a normal diet (the control normal group), a regular diet supplemented with kiwifruit at two concentrations (i.e., 1.86 g/kg and 3.73 g/kg), a HFD comprised of 15% butterfat + 0.05% cholesterol (the control high-fat group), and a HFD supplemented with kiwifruit at two concentrations (i.e., 1.86 and 3.73 g/kg) for 8 weeks. Results: The results showed that supplementation of kiwifruit to the HFD increased the levels of HDL-C and remarkably reduced the concentrations of oxidized low-density lipoprotein (ox-LDL) and malondialdehyde (MDA) compared with the control-HF group. In addition, the paraoxonase activity of PON1 significantly increased in HFD supplemented with kiwifruit (1.86 g/kg), and finally, arylesterase (ARE) activity increased in all treated groups when compared with untreated groups. Conclusion: Our findings suggested that kiwifruit can improve the lipid profile and prevent oxidative stress-induced by lipid peroxidation in hamsters receiving HFD, thus increasing the ARE and paraoxonase activities of PON1.


PLoS ONE ◽  
2016 ◽  
Vol 11 (7) ◽  
pp. e0159568 ◽  
Author(s):  
Yang Bai ◽  
Zhaojing Dong ◽  
Qianwen Shang ◽  
Hui Zhao ◽  
Liyang Wang ◽  
...  

2018 ◽  
Vol 19 (12) ◽  
pp. 3903 ◽  
Author(s):  
Xiaofei Zhu ◽  
Jingyi Yang ◽  
Wenjuan Zhu ◽  
Xiaoxiao Yin ◽  
Beibei Yang ◽  
...  

The natural compound berberine has been reported to exhibit anti-diabetic activity and to improve disordered lipid metabolism. In our previous study, we found that such compounds upregulate expression of sirtuin 1—a key molecule in caloric restriction, it is, therefore, of great interest to examine the lipid-lowering activity of berberine in combination with a sirtuin 1 activator resveratrol. Our results showed that combination of berberine with resveratrol had enhanced hypolipidemic effects in high fat diet-induced mice and was able to decrease the lipid accumulation in adipocytes to a level significantly lower than that in monotherapies. In the high fat diet-induced hyperlipidemic mice, combination of berberine (25 mg/kg/day, oral) with resveratrol (20 mg/kg/day, oral) reduced serum total cholesterol by 27.4% ± 2.2%, and low-density lipoprotein-cholesterol by 31.6% ± 3.2%, which was more effective than that of the resveratrol (8.4% ± 2.3%, 6.6% ± 2.1%) or berberine (10.5% ± 1.95%, 9.8% ± 2.58%) monotherapy (p < 0.05 for both). In 3T3-L1 adipocytes, the treatment of 12 µmol/L or 20 µmol/L berberine combined with 25 µmol/L resveratrol showed a more significant inhibition of lipid accumulation observed by Oil red O stain compared with individual compounds. Moreover, resveratrol could increase the amount of intracellular berberine in hepatic L02 cells. In addition, the combination of berberine with resveratrol significantly increases the low-density-lipoprotein receptor expression in HepG2 cells to a level about one-fold higher in comparison to individual compound. These results implied that the enhanced effect of the combination of berberine with resveratrol on lipid-lowering may be associated with upregulation of low-density-lipoprotein receptor, and could be an effective therapy for hyperlipidemia in some obese-associated disease, such as type II diabetes and metabolic syndrome.


PLoS ONE ◽  
2018 ◽  
Vol 13 (3) ◽  
pp. e0193737 ◽  
Author(s):  
Sarvenaz Metghalchi ◽  
Marie Vandestienne ◽  
Yacine Haddad ◽  
Bruno Esposito ◽  
Julien Dairou ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document