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Flaxseed Oil Containing α -Linolenic Acid Ester of Plant Sterol Improved Atherosclerosis in ApoE Deficient Mice.

Han H, Yan P, Chen L, Luo C, Gao H, Deng Q, Zheng M, Shi Y, Liu L - Oxid Med Cell Longev (2015)

Bottom Line: Dietary α-linolenic acid in flaxseed oil is associated with a reduction in cardiovascular events through its hypolipidemic and anti-inflammation properties.Results demonstrated that flaxseed oil containing ALA-PS was synergistically interaction in ameliorating atherosclerosis as well as optimizing overall lipid levels, inhibiting inflammation and reducing oxidative stress.These data were associated with the modification effects on expression levels of genes involved in lipid metabolism (PPARα, HMGCR, and SREBPs), inflammation (IL-6, TNF, MCP-1, and VCAM-1), and oxidative stress (NADPH oxidase).

View Article: PubMed Central - PubMed

Affiliation: Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China ; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

ABSTRACT
Plant sterols (PS) have potential preventive function in atherosclerosis due to their cholesterol-lowering ability. Dietary α-linolenic acid in flaxseed oil is associated with a reduction in cardiovascular events through its hypolipidemic and anti-inflammation properties. This study was designed to evaluate the effects of flaxseed oil containing α-linolenic acid ester of PS (ALA-PS) on atherosclerosis and investigate the underlying mechanisms. C57BL/6 mice were administered a regular diet and apoE knockout (apoE-KO) mice were given a high fat diet alone or supplemented with 5% flaxseed oil with or without 3.3% ALA-PS for 18 weeks. Results demonstrated that flaxseed oil containing ALA-PS was synergistically interaction in ameliorating atherosclerosis as well as optimizing overall lipid levels, inhibiting inflammation and reducing oxidative stress. These data were associated with the modification effects on expression levels of genes involved in lipid metabolism (PPARα, HMGCR, and SREBPs), inflammation (IL-6, TNF, MCP-1, and VCAM-1), and oxidative stress (NADPH oxidase).

No MeSH data available.


Related in: MedlinePlus

Effects of FO+ALA-PS on mRNA and protein expressions of hepatic HMGCR (a-b), SREBP-2 (c-d), PPARα (e-f), and SREBP-1c (g-h) in mice. After intervention by flaxseed oil with ALA-PS for 18 weeks, total RNA was extracted from liver of mice by Trizol. HMGCR, SREBP-2 PPARα, and SREBP-1c mRNA expressions were analyzed by real-time RT-PCR. The mRNA of β-actin was quantified as an endogenous control. Hepatic lysates were prepared and immunoblotted with corresponding antibody, respectively. Blotting with anti-β-actin was used as a protein loading control. HMGCR, SREBP-2, PPARα, and SREBP-1c are presented as fold change relative to control. Representative immunoblots are shown. Values are given as mean ± standard deviation of the mean (n = 3). aP < 0.05 versus the control; bP < 0.05 versus the HFD group; cP < 0.05 versus the FO group.
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fig3: Effects of FO+ALA-PS on mRNA and protein expressions of hepatic HMGCR (a-b), SREBP-2 (c-d), PPARα (e-f), and SREBP-1c (g-h) in mice. After intervention by flaxseed oil with ALA-PS for 18 weeks, total RNA was extracted from liver of mice by Trizol. HMGCR, SREBP-2 PPARα, and SREBP-1c mRNA expressions were analyzed by real-time RT-PCR. The mRNA of β-actin was quantified as an endogenous control. Hepatic lysates were prepared and immunoblotted with corresponding antibody, respectively. Blotting with anti-β-actin was used as a protein loading control. HMGCR, SREBP-2, PPARα, and SREBP-1c are presented as fold change relative to control. Representative immunoblots are shown. Values are given as mean ± standard deviation of the mean (n = 3). aP < 0.05 versus the control; bP < 0.05 versus the HFD group; cP < 0.05 versus the FO group.

Mentions: The intervention of flaxseed oil alleviated the rise of TG induced by HFD in serum and liver while a much larger decrease in TG was observed in FO+ALA-PS group. Although flaxseed oil feeding alone elevated serum HDL-C, it had no effect on LDL-C and TC. Combination treatment not only apparently reduced LDL-C and TC but also increased the concentration of HDL-C (Table 2). To investigate the underlying molecular mechanism by which dietary FO+ALA-PS modulates lipid metabolism, gene and protein expressions of the major factors involved in hepatic cholesterol homoeostasis, fatty acid catabolism, and synthesis were detected. As illustrated in Figure 3, mRNA and protein expressions of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and sterol regulatory element binding protein 2 (SREBP-2) were found to be statistically decreased in FO+ALA-PS-treated but not FO-treated animals, as compared to those in HFD-fed animals. In addition, flaxseed oil intervention elevated peroxisome proliferator-activated receptor α (PPARα) and reduced sterol regulatory element-binding protein 1c (SREBP-1c), respectively. A more pronounced effect was achieved by FO+ALA-PS application.


Flaxseed Oil Containing α -Linolenic Acid Ester of Plant Sterol Improved Atherosclerosis in ApoE Deficient Mice.

Han H, Yan P, Chen L, Luo C, Gao H, Deng Q, Zheng M, Shi Y, Liu L - Oxid Med Cell Longev (2015)

Effects of FO+ALA-PS on mRNA and protein expressions of hepatic HMGCR (a-b), SREBP-2 (c-d), PPARα (e-f), and SREBP-1c (g-h) in mice. After intervention by flaxseed oil with ALA-PS for 18 weeks, total RNA was extracted from liver of mice by Trizol. HMGCR, SREBP-2 PPARα, and SREBP-1c mRNA expressions were analyzed by real-time RT-PCR. The mRNA of β-actin was quantified as an endogenous control. Hepatic lysates were prepared and immunoblotted with corresponding antibody, respectively. Blotting with anti-β-actin was used as a protein loading control. HMGCR, SREBP-2, PPARα, and SREBP-1c are presented as fold change relative to control. Representative immunoblots are shown. Values are given as mean ± standard deviation of the mean (n = 3). aP < 0.05 versus the control; bP < 0.05 versus the HFD group; cP < 0.05 versus the FO group.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4477243&req=5

fig3: Effects of FO+ALA-PS on mRNA and protein expressions of hepatic HMGCR (a-b), SREBP-2 (c-d), PPARα (e-f), and SREBP-1c (g-h) in mice. After intervention by flaxseed oil with ALA-PS for 18 weeks, total RNA was extracted from liver of mice by Trizol. HMGCR, SREBP-2 PPARα, and SREBP-1c mRNA expressions were analyzed by real-time RT-PCR. The mRNA of β-actin was quantified as an endogenous control. Hepatic lysates were prepared and immunoblotted with corresponding antibody, respectively. Blotting with anti-β-actin was used as a protein loading control. HMGCR, SREBP-2, PPARα, and SREBP-1c are presented as fold change relative to control. Representative immunoblots are shown. Values are given as mean ± standard deviation of the mean (n = 3). aP < 0.05 versus the control; bP < 0.05 versus the HFD group; cP < 0.05 versus the FO group.
Mentions: The intervention of flaxseed oil alleviated the rise of TG induced by HFD in serum and liver while a much larger decrease in TG was observed in FO+ALA-PS group. Although flaxseed oil feeding alone elevated serum HDL-C, it had no effect on LDL-C and TC. Combination treatment not only apparently reduced LDL-C and TC but also increased the concentration of HDL-C (Table 2). To investigate the underlying molecular mechanism by which dietary FO+ALA-PS modulates lipid metabolism, gene and protein expressions of the major factors involved in hepatic cholesterol homoeostasis, fatty acid catabolism, and synthesis were detected. As illustrated in Figure 3, mRNA and protein expressions of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and sterol regulatory element binding protein 2 (SREBP-2) were found to be statistically decreased in FO+ALA-PS-treated but not FO-treated animals, as compared to those in HFD-fed animals. In addition, flaxseed oil intervention elevated peroxisome proliferator-activated receptor α (PPARα) and reduced sterol regulatory element-binding protein 1c (SREBP-1c), respectively. A more pronounced effect was achieved by FO+ALA-PS application.

Bottom Line: Dietary α-linolenic acid in flaxseed oil is associated with a reduction in cardiovascular events through its hypolipidemic and anti-inflammation properties.Results demonstrated that flaxseed oil containing ALA-PS was synergistically interaction in ameliorating atherosclerosis as well as optimizing overall lipid levels, inhibiting inflammation and reducing oxidative stress.These data were associated with the modification effects on expression levels of genes involved in lipid metabolism (PPARα, HMGCR, and SREBPs), inflammation (IL-6, TNF, MCP-1, and VCAM-1), and oxidative stress (NADPH oxidase).

View Article: PubMed Central - PubMed

Affiliation: Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China ; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

ABSTRACT
Plant sterols (PS) have potential preventive function in atherosclerosis due to their cholesterol-lowering ability. Dietary α-linolenic acid in flaxseed oil is associated with a reduction in cardiovascular events through its hypolipidemic and anti-inflammation properties. This study was designed to evaluate the effects of flaxseed oil containing α-linolenic acid ester of PS (ALA-PS) on atherosclerosis and investigate the underlying mechanisms. C57BL/6 mice were administered a regular diet and apoE knockout (apoE-KO) mice were given a high fat diet alone or supplemented with 5% flaxseed oil with or without 3.3% ALA-PS for 18 weeks. Results demonstrated that flaxseed oil containing ALA-PS was synergistically interaction in ameliorating atherosclerosis as well as optimizing overall lipid levels, inhibiting inflammation and reducing oxidative stress. These data were associated with the modification effects on expression levels of genes involved in lipid metabolism (PPARα, HMGCR, and SREBPs), inflammation (IL-6, TNF, MCP-1, and VCAM-1), and oxidative stress (NADPH oxidase).

No MeSH data available.


Related in: MedlinePlus