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Lutein Prevents High Fat Diet-Induced Atherosclerosis in ApoE-Deficient Mice by Inhibiting NADPH Oxidase and Increasing PPAR Expression

Abstract

Epidemiological and experimental studies provide supportive evidence that lutein, a major carotenoid, may act as a chemopreventive agent against atherosclerosis, although the underlying molecular mechanisms are not well understood. The main aim of this study was to investigate the effects of lutein on the alleviation of atherosclerosis and its molecular mechanisms involved in oxidative stress and lipid metabolism. Male apolipoprotein E knockout mice (n = 55) were fed either a normal chow diet or a high fat diet (HFD) supplemented with or without lutein for 24 weeks. The results showed that a HFD induced atherosclerosis formation, lipid metabolism disorders and oxidative stress, but noticeable improvements were observed in the lutein treated group. Additionally, lutein supplementation reversed the decreased protein expression of aortic heme oxygenase-1 and increased the mRNA and protein expressions of aortic nicotinamide-adenine dinucleotide phosphate oxidase stimulated by a HFD. Furthermore, the decreased mRNA and protein expression levels of hepatic peroxisome proliferator-activated receptor-α, carnitine palmitoyltransferase 1A, acyl CoA oxidase 1, low density lipoprotein receptors and scavenger receptor class B type I observed in mice with atherosclerosis were markedly enhanced after treatment with lutein. Taken together, these data add new evidence supporting the anti-atherogenic properties of lutein and describing its mechanisms of action in atherosclerosis prevention, including oxidative stress and lipid metabolism improvements.

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Abbreviations

ACOX1:

Acyl CoA oxidase 1

AIP:

Atherogenic index of plasma

CPT1A:

Carnitine palmitoyltransferase 1A

HDL-C:

High density lipoprotein cholesterol

HO-1:

Heme oxygenase-1

LDL-C:

Low density lipoprotein cholesterol

LDLr:

Low density lipoprotein receptor

MDA:

Malondialdehyde

NADPH:

Nicotinamide-adenine dinucleotide phosphate

NHDL-C:

Non-high density lipoprotein cholesterol

PPAR:

Peroxisome proliferator-activated receptors

ROS:

Reactive oxygen species

SR-BI:

Scavenger receptor class B type I

SOD:

Superoxide dismutase

TC:

Total cholesterol

TAG:

Triacylglycerol

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Acknowledgments

We are grateful to Wenzhong Wu and Yuan Huang of InnoBio Co., Ltd, Dalian, China for supplying the lutein samples. This work was supported by the National High Technology Research and Development Program of China (2010AA023003) and the National Natural Science Foundation of China (NSFC-81172657).

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The authors have declared that no competing interests exist.

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Correspondence to Liping Hao.

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Han, H., Cui, W., Wang, L. et al. Lutein Prevents High Fat Diet-Induced Atherosclerosis in ApoE-Deficient Mice by Inhibiting NADPH Oxidase and Increasing PPAR Expression. Lipids 50, 261–273 (2015). https://doi.org/10.1007/s11745-015-3992-1

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  • DOI: https://doi.org/10.1007/s11745-015-3992-1

Keywords

  • Lutein
  • Atherosclerosis
  • Heme oxygenase-1 (HO-1)
  • Nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase
  • Peroxisome proliferator-activated receptor-α (PPARα)
  • Low density lipoprotein receptors (LDLr)
  • Scavenger receptor class B type I (SR-BI)