Regulation of mevalonate synthesis in low density lipoprotein receptor knockout mice fed n‐3 or n‐6 polyunsaturated fatty acids

El-Sohemy, Ahmed; Archer, Michael C.

doi:10.1007/s11745-999-0455-8

Cited by 31 publications

(8 citation statements)

References 29 publications

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“…Further, EPA and DHA incorporation into membrane rafts (MRs) reduces total cholesterol content and ultimately enhances apoptosis in epithelial, prostate and cancer cells via Akt inactivation [131]. Antiproliferative action and apoptosis has also been demonstrated by EPA and DHA through inhibition of HMG-CoA reductase [132], which inhibits the mevalonate pathway and, ultimately, the function of oncogenic forms of Ras.…”

Section: Differential Effects Of N-3 Pufa In Cancermentioning

confidence: 99%

Are all n-3 polyunsaturated fatty acids created equal?

2009

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N-3 Polyunsaturated fatty acids have been shown to have potential beneficial effects for chronic diseases including cancer, insulin resistance and cardiovascular disease. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in particular have been studied extensively, whereas substantive evidence for a biological role for the precursor, alpha-linolenic acid (ALA), is lacking. It is not enough to assume that ALA exerts effects through conversion to EPA and DHA, as the process is highly inefficient in humans. Thus, clarification of ALA's involvement in health and disease is essential, as it is the principle n-3 polyunsaturated fatty acid consumed in the North American diet and intakes of EPA and DHA are typically very low. There is evidence suggesting that ALA, EPA and DHA have specific and potentially independent effects on chronic disease. Therefore, this review will assess our current understanding of the differential effects of ALA, EPA and DHA on cancer, insulin resistance, and cardiovascular disease. Potential mechanisms of action will also be reviewed. Overall, a better understanding of the individual role for ALA, EPA and DHA is needed in order to make appropriate dietary recommendations regarding n-3 polyunsaturated fatty acid consumption.

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Section: Differential Effects Of N-3 Pufa In Cancermentioning

confidence: 99%

Are all n-3 polyunsaturated fatty acids created equal?

2009

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“…Similar to statins, AA, EPA, and DHA are useful in the treatment of hyperlipidemias, have anti-proliferative action on tumor cells both in vitro and in vivo, bind to DNA and regulate the expression of genes and oncogenes. More importantly, PUFAs are also potent inhibitors of the HMG-CoA reductase enzyme [58,59]. Statins have the ability to enhance plasma AA concentrations and decrease the ratio of EPA to AA significantly [60].…”

Section: Pufas Decrease Hmg-coa Reductase Activ-itymentioning

confidence: 99%

Essential Fatty Acids - A Review

Das¹

2006

CPB

345

208

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Essential fatty acids (EFAs): cis-linoleic acid (LA) and alpha-linolenic acid (ALA) are essential for humans and their deficiency is rare in humans due to their easy availability in diet. EFAs are metabolized to their respective long-chain metabolites: dihomo-gamma-linolenic acid (DGLA), and arachidonic acid (AA) from LA; and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from ALA. Some of these long-chain metabolites form precursors to respective prostaglandins (PGs), thromboxanes (TXs), and leukotrienes (LTs), lipoxins (LXs) and resolvins. EFAs and their metabolites may function as endogenous angiotensin converting enzyme and HMG-CoA reductase inhibitors, nitric oxide enhancers, anti-hypertensives, and anti-atherosclerotic molecules. EFAs react with nitric oxide (NO) to yield respective nitroalkene derivatives that have cell-signaling actions via ligation and activation of peroxisome proliferator-activated receptors (PPARs). In several diseases such as obesity, hypertension, diabetes mellitus, coronary heart disease, alcoholism, schizophrenia, Alzheimer's disease, atherosclerosis, and cancer the metabolism of EFAs is altered. Thus, EFAs and their derivatives have significant clinical implications.

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“…PUFAs are also potent inhibitors of the HMG-CoA reductase enzyme [106,[375][376][377]. Statins, which are HMGCoA reductase enzyme inhibitors, have the ability to enhance plasma AA concentrations and decrease the ratio of EPA to AA significantly [375][376][377] and PUFAs seem to be the mediators of many actions of statins that may explain the beneficial actions of both PUFAs and statins in the prevention and treatment of atherosclerosis and CHD.…”

Section: Effects On Ace and Hmg-coa Enzymesmentioning

confidence: 99%

Beneficial Actions of Polyunsaturated Fatty Acids in Cardiovascular Diseases: But, How and Why?

Das¹

2008

CNF

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Omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and to a limited extent -6 fatty acids: arachidonic acid (AA), -linolenic acid (GLA) and dihomo-GLA (DGLA), prevent cardiovascular disease, thrombosis and atherosclerosis, reduce cardiac arrhythmias, lower plasma cholesterol and triglycerides, lower high blood pressure and improve endothelial function. These beneficial actions of the fatty acids could be attributed to their ability to augment endothelial nitric oxide generation, inhibit HMG-CoA reductase and angiotensin converting enzyme (ACE) activities, block the production of pro-inflammatory cytokines, and modulate telomerase activity. AA, EPA, and DHA form precursors to anti-inflammatory molecules: lipoxins and resolvins that help in wound healing, inhibit the actions of pro-inflammatory eicosanoids, and suppress the production of free radicals and enhance nitric oxide (NO) generation. In addition, these fatty acids react with NO and NO-derived reactive nitrogen species to form nitroalkene derivative of fatty acids called as nitrolipids. Nitrolipids serve as potent ligands for peroxisome proliferator activated receptors (PPARs), inhibit platelet activation through elevation of cyclic AMP levels; suppress superoxide generation, degranulation, and integrin expression by human neutrophils, and induce vasorelaxation in a concentration dependent manner by releasing NO. Nitrolipids are formed at the sites of inflammation in significant amounts and increased by oxidative inflammatory reactions. Furthermore, -3 and -6 fatty acids interact with each other to enhance the formation of prostaglandin E 1 (PGE 1 ), prostacyclin (PGI 2 ), and PGI 3 , which are potent platelet anti-aggregators and vasodilators. Thus, GLA, DGLA, AA, EPA, and DHA when present in optimum amounts in the tissues, especially in endothelial cells, myocardium, platelets, and neutrophils, may aid in the prevention of cardiovascular diseases.

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Regulation of mevalonate synthesis in low density lipoprotein receptor knockout mice fed n‐3 or n‐6 polyunsaturated fatty acids

Cited by 31 publications

References 29 publications

Are all n-3 polyunsaturated fatty acids created equal?

Are all n-3 polyunsaturated fatty acids created equal?

Essential Fatty Acids - A Review

Beneficial Actions of Polyunsaturated Fatty Acids in Cardiovascular Diseases: But, How and Why?

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