Eicosapentaenoic acid lowers plasma and liver cholesterol levels in the presence of peroxisome proliferators-activated receptor alpha

Sugiyama, Eiko; Ishikawa, Yasuko; Li, Yufeng; Kagai, Tomoko; Nobayashi, Misaki; Tanaka, Naoki; Kamijo, Yuji; Yokoyama, Shinichi; Hara, Atsushi; Aoyama, Toshifumi

doi:10.1016/j.lfs.2008.04.011

Cited by 34 publications

(32 citation statements)

References 67 publications

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“…On the other hand, hypothyroidism induced a marked increase in liver expression of PPARa. Apparently, the control of serum lipids by n-3 PUFA involves different signaling pathways, a PPARadependent one for cholesterol and another, PPARa independent for triglycerides (Dallongeville et al 2001, Sugiyama et al 2008, Wakutsu et al 2010. Indeed, our finding of marked increase in PPARa protein content in the liver of hypothyroid rats may justify the normalization of serum cholesterol in hypothyroid livers and in addition supports those previous reports arguing that the hypotriglyceridemic effect of n-3 PUFA is not dependent on PPARa.…”

Section: Discussionsupporting

confidence: 87%

“…The hypolipidemic effect of the FO has been explained by several mechanisms. Most of the FO effects were exerted via PPARa (Sugiyama et al 2008) and other hepatic transcriptional factors such as sterol regulatory element-binding protein-1 (Yahagi et al 1999). In addition, the involvement of other nuclear receptors, such as retinoic X receptor (Suzuki et al 2009) and LXR (Howell et al 2009), has also been reported.…”

Section: Introductionmentioning

confidence: 99%

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Thyroid hormone contributes to the hypolipidemic effect of polyunsaturated fatty acids from fish oil: in vivo evidence for cross talking mechanisms

Souza¹,

Cordeiro²,

Oliveira³

et al. 2011

Journal of Endocrinology

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n-3 polyunsaturated fatty acids (n-3 PUFA) from fish oil (FO) exert important lipid-lowering effects, an effect also ascribed to thyroid hormones (TH) and TH receptor b1 (TRb1)-specific agonists. n-3 PUFA effects are mediated by nuclear receptors, such as peroxisome proliferator-activated receptors (PPAR) and others. In this study, we investigated a role for TH signaling in n-3 PUFA effects. Euthyroid and hypothyroid adult rats (methimazole-treated for 5 weeks) received FO or soybean oil (control) by oral administration for 3 weeks. In euthyroid rats, FO treatment reduced serum triglycerides and cholesterol, diminished body fat, and increased protein content of the animals. In addition, FO-treated rats exhibited higher liver expression of TRb1 and mitochondrial a-glycerophosphate dehydrogenase (mGPD), at protein and mRNA levels, but no alteration of glutathione S-transferase or type 1 deiodinase. In hypothyroid condition, FO induced reduction in serum cholesterol and increase in body protein content, but lost the ability to reduce triglycerides and body fat, and to induce TRb1 and mGDP expression. FO did not change PPARa liver abundance regardless of thyroid state; however, hypothyroidism led to a marked increase in PPARa liver content but did not alter TRb1 or TRa expression. The data suggest that part of the effect of n-3 PUFA from FO on lipid metabolism is dependent on TH signaling in specific steps and together with the marked upregulation of PPARa in liver of hypothyroid rats suggest important in vivo consequences of the cross-talking between those fatty acids and TH pathways in liver metabolism.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Thyroid hormone contributes to the hypolipidemic effect of polyunsaturated fatty acids from fish oil: in vivo evidence for cross talking mechanisms

Souza¹,

Cordeiro²,

Oliveira³

et al. 2011

Journal of Endocrinology

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“…The fact that, similarly to our data, PPARα gene expression was not induced in EPA-fed mice in the experiment of Sugiyama et al (2008) was surprising. PPARα mRNA in the n-3 PUFA-fed rats was similarly unaltered in the experiment of Lu et al (2011).…”

Section: Discussionsupporting

confidence: 86%

Effect of dietary eicosapentaenoic and docosahexaenoic acid on expression of rat liver genes controlling cholesterol homeostasis and on plasma cholesterol level

Komprda¹,

Zorníková²,

Knoll³

et al. 2014

Czech J. Anim. Sci.

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A hypothesis that eicosapentaenoic acid + docosahexaenoic acid (EPA+DHA) lower plasma cholesterol via increased expression of the Insig-1 gene with ensuing decrease of expression of genes coding for 3-hydroxy-3-methyl-glutaryl-CoA reductase (Hmgcr) and low density lipoprotein receptor (Ldlr) was tested in rats fed a diet with 3% of fish oil (FO). Expression of the Insig-1 gene in the liver of the FO-fed rats was 730% (P < 0.05) of the control. However, contrary to the hypothesis, expression of the Hmgcr gene and Ldlr gene was 165% and 210% of the control (P > 0.05). Nevertheless, FO in the diet decreased (P < 0.05) plasma cholesterol of rats by 10% (from 1.19 to 1.07 mmol/l); it was therefore concluded that the cholesterol-lowering effect of EPA+DHA is at least partly based on mechanisms other than tested in the present experiment.

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Section: Linkage Between Ppar and Cox-2mentioning

confidence: 99%

“…For example, PPARα agonists, such as fibrates and thiazolidine derivatives, are used to treat dyslipidemia and diabetes, respectively. Moreover, eicosapentaenoic acid, a natural ligand for PPARα, has been used as a hypolipidemic drug and has been reported to lower plasma and liver cholesterol levels in a PPARα-dependent manner (Sugiyama et al, 2008).PPARs are also involved in the control of COX-2 expression. COX is the rate-limiting enzyme in prostaglandin (PG) biosynthesis, and its activity is inhibited by non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, indomethacin and ibuprofen (Fig.…”

mentioning

confidence: 99%

Evaluation of Food-derived Functional Ingredients According to Activation of PPAR and Suppression of COX-2 Expression

Nakata

Takizawa

Takai

et al. 2013

FSTR

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The peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors belonging to the nuclear receptor family. They are considered molecular targets for the prevention of lifestyle-related diseases and are involved in the control of cyclooxygenase (COX)-2 expression. COX-2, the rate-limiting enzyme in prostaglandin biosynthesis, plays a key role in inflammation and circulatory homeostasis, and its expression is partly controlled by PPAR. We have identified several natural chemicals, such as resveratrol, that activate PPARs and suppress COX-2 expression. In this review, we provide an evaluation of food-derived functional ingredients that target PPARs and COX-2.Keywords: PPAR, COX-2, resveratrol, essential oil, anti-lifestyle-related disease *To whom correspondence should be addressed. E-mail: inoue@cc.nara-wu.ac.jp IntroductionThe prevention of lifestyle-related diseases, such as cardiovascular disease, diabetes, and stroke, is of worldwide interest. Individuals tend to focus not only on drug therapy for prevention of these diseases, but also on the functionality of natural chemicals found in food and beverages, such as polyphenols and their polymers. A growing body of evidence supports the theory that polyphenolic compounds have activities that maintain health. Epidemiological studies have demonstrated that dietary polyphenol intake, e.g., red wine consumption, may improve endothelial function and reduce risk for cardiovascular diseases (Stoclet et al., 2004; Cordova et al., 2005;Opie et al., 2007). Although there have been numerous studies investigating food-derived functional components, the molecular mechanisms for their actions remain to be determined. We found that several natural food-derived components, such as resveratrol, activate peroxisome proliferator-activated receptors (PPARs) and suppress expression of cyclooxygenase (COX)-2. These two properties targeted specifically to PPARs and COX-2 will be important for evaluating food-derived functional components. This review discusses the effects of food-derived functional components on PPARs and COX-2, and evaluates novel functions of these compounds in relation to prevention of lifestyle-related diseases. Linkage Between PPAR and COX-2PPARs are members of a nuclear receptor family of ligand-dependent transcription factors (Mangelsdolf et al., 1995). The PPAR subfamily comprises three isotypes, PPARα, β/δ and γ, which play various roles in lipid and carbohydrate metabolism, cell proliferation and differentiation, and inflammation; they are considered molecular targets in the prevention of lifestyle-related diseases (Michalik et al., 2006;Sonoda et al., 2008). For example, PPARα agonists, such as fibrates and thiazolidine derivatives, are used to treat dyslipidemia and diabetes, respectively. Moreover, eicosapentaenoic acid, a natural ligand for PPARα, has been used as a hypolipidemic drug and has been reported to lower plasma and liver cholesterol levels in a PPARα-dependent manner (Sugiyama et al., 2008).PPARs are also invo...

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Eicosapentaenoic acid lowers plasma and liver cholesterol levels in the presence of peroxisome proliferators-activated receptor alpha

Cited by 34 publications

References 67 publications

Thyroid hormone contributes to the hypolipidemic effect of polyunsaturated fatty acids from fish oil: in vivo evidence for cross talking mechanisms

Thyroid hormone contributes to the hypolipidemic effect of polyunsaturated fatty acids from fish oil: in vivo evidence for cross talking mechanisms

Effect of dietary eicosapentaenoic and docosahexaenoic acid on expression of rat liver genes controlling cholesterol homeostasis and on plasma cholesterol level

Evaluation of Food-derived Functional Ingredients According to Activation of PPAR and Suppression of COX-2 Expression

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