Parent Fatty Acids Research Articles

Lipidic Protic Ionic Liquid Crystals

Protic ionic liquids (PILs) based on lipidic compounds have a range of industrial applications, revealing the potential of oil chemistry as a sustainable basis for the synthesis of ionic liquids. PILs of fatty acids with ethanolamines are here disclosed to form ionic liquid crystals, and their mixtures with the parent fatty acids and ethanolamines display a lyotropic behavior. Aiming at characterizing their rheologic and phase behavior, four ethanolamine carboxylates and the mixtures used for their synthesis through a Bronsted acid–base reaction are investigated. Their phase diagrams present a complex multiphase profile, exhibiting lyotropic mesophases as well as solid–liquid biphasic domains with a congruent melting behavior. These PILs present a high self-assembling ability and a non-Newtonian behavior with yield stress in the liquid crystal mesophase. The appearance of lamellar and hexagonal structures, with probably normal and inverted configurations in the mixtures, due to the formation of the PILs i...

Comparison of free serum oxylipin concentrations in hyper- vs. normolipidemic men

Oxylipins, the oxidation products of unsaturated fatty acids (FA), are potent endogenous mediators being involved in the regulation of various biological processes such as inflammation, pain and blood coagulation. Compared to oxylipins derived from arachidonic acid (AA) by cyclooxygenase action, i.e. prostanoides, only limited information is available about the endogenous levels of hydroxy-, epoxy- and dihydroxy-FA of linoleic acid (LA), AA, α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in humans. Particularly, it is unknown how metabolic disorders affect endogenous oxylipin levels in humans. Therefore, in the present study we compared the serum concentrations of 44 oxylipins in 20 normolipidemic with 20 hyperlipidemic (total cholesterol >200mg/dl; LDL-C>130mg/dl; TG>150mg/dl) men (age 29–51y). The serum concentration varied strongly among subjects. For most hydroxy-, epoxy- and dihydroxy-FA the concentrations were comparable to those in plasma reported in earlier studies. Despite the significant change in blood lipid levels the hyperlipidemic group showed only minor differences in oxylipin levels. The hyperlipidemic subjects had a slightly higher serum concentration of 8,9-DiHETrE, 5-HEPE, 10,11-DiHDPE, and a lower concentration of 12,13-DiHOME, 12-HETE, 9,10-DiHODE, and 12,13-DiHODE compared to normolipidemic subjects. Overall the hydroxy-, epoxy- and dihydroxy-FA levels were not changed suggesting that mild combined hyperlipidemia has no apparent effect on the concentration of circulating oxylipins. By contrast, serum levels of several hydroxy-, epoxy-, and dihydroxy-FA are dependent on the individual status of the parent FA. Particularly, a strong correlation between the EPA content in the erythrocyte membrane and the serum concentration of EPA derived oxylipins was observed. Given that the synthesis of EPA from other n-3 FA in humans is low; this suggests that oxylipin levels can be directly influenced by the diet.

Scientific Opinion on the substantiation of a health claim related to alpha linolenic acid and contribution to brain and nerve tissue development pursuant to Article 14 of Regulation (EC) No 1924/2006

Following an application from HiPP GmbH & Co Vertrieb KG submitted pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of Germany, the Panel on Dietetic Products, Nutrition and Allergies was asked to deliver an opinion on the scientific substantiation of a health claim related to alpha-linolenic acid and contribution to brain and nerve tissue development. Alpha-linolenic acid is considered to be sufficiently characterised. Contribution to brain and nerve tissue development is considered to be a beneficial physiological effect. Alpha-linolenic acid is the parent fatty acid of the longer chain n 3 polyunsaturated fatty acids, including docosahexaenoic acid, which is the major structural lipid in brain tissue and the central nervous system. Deficiency of alpha-linolenic acid results in adverse clinical symptoms including neurological abnormalities and poor growth. The Panel notes that for normal brain and nerve tissue development, alpha-linolenic acid, like other essential nutrients, is needed in adequate amounts. The Panel concludes that a cause and effect relationship has been established between the dietary intake of alpha-linolenic acid and contribution to brain and nerve tissue development. The following wording reflects the scientific evidence: “Alpha-linolenic acid, an essential fatty acid, contributes to brain and nerve tissue development.” The target population is infants and children up to three years. © European Food Safety Authority, 2011

Lipid redistribution by α-linolenic acid-rich chia seed inhibits stearoyl-CoA desaturase-1 and induces cardiac and hepatic protection in diet-induced obese rats

Chia seeds contain the essential fatty acid, α-linolenic acid (ALA). This study has assessed whether chia seeds attenuated the metabolic, cardiovascular and hepatic signs of a high-carbohydrate, high-fat (H) diet [carbohydrates, 52% (wt/wt); fat, 24% (wt/wt) with 25% (wt/vol) fructose in drinking water] in rats. Diets of the treatment groups were supplemented with 5% chia seeds after 8 weeks on H diet for a further 8 weeks. Compared with the H rats, chia seed-supplemented rats had improved insulin sensitivity and glucose tolerance, reduced visceral adiposity, decreased hepatic steatosis and reduced cardiac and hepatic inflammation and fibrosis without changes in plasma lipids or blood pressure. Chia seeds induced lipid redistribution with lipid trafficking away from the visceral fat and liver with an increased accumulation in the heart. The stearoyl-CoA desaturase-1 products were depleted in the heart, liver and the adipose tissue of chia seed-supplemented rats together with an increase in the substrate concentrations. The C18:1 trans-7 was preferentially stored in the adipose tissue; the relatively inert C18:1n-9 was stored in sensitive organs such as liver and heart and C18:2n-6, the parent fatty acid of the n-6 pathway, was preferentially metabolized. Thus, chia seeds as a source of ALA induce lipid redistribution associated with cardioprotection and hepatoprotection.

Naturally occurring monoepoxides of eicosapentaenoic acid and docosahexaenoic acid are bioactive antihyperalgesic lipids

Beneficial physiological effects of long-chain n-3 polyunsaturated fatty acids are widely accepted but the mechanism(s) by which these fatty acids act remains unclear. Herein, we report the presence, distribution, and regulation of the levels of n-3 epoxy-fatty acids by soluble epoxide hydrolase (sEH) and a direct antinociceptive role of n-3 epoxy-fatty acids, specifically those originating from docosahexaenoic acid (DHA). The monoepoxides of the C18:1 to C22:6 fatty acids in both the n-6 and n-3 series were prepared and the individual regioisomers purified. The kinetic constants of the hydrolysis of the pure regioisomers by sEH were measured. Surprisingly, the best substrates are the mid-chain DHA epoxides. We also demonstrate that the DHA epoxides are present in considerable amounts in the rat central nervous system. Furthermore, using an animal model of pain associated with inflammation, we show that DHA epoxides, but neither the parent fatty acid nor the corresponding diols, selectively modulate nociceptive pathophysiology. Our findings support an important function of epoxy-fatty acids in the n-3 series in modulating nociceptive signaling. Consequently, the DHA and eicosapentaenoic acid epoxides may be responsible for some of the beneficial effects associated with dietary n-3 fatty acid intake.

Glucose regulates fatty acid binding protein interaction with lipids and peroxisome proliferator-activated receptor α

Although the pathophysiology of diabetes is characterized by elevated levels of glucose and long-chain fatty acids (LCFA), nuclear mechanisms linking glucose and LCFA metabolism are poorly understood. As the liver fatty acid binding protein (L-FABP) shuttles LCFA to the nucleus, where L-FABP directly interacts with peroxisome proliferator-activated receptor-α (PPARα), the effect of glucose on these processes was examined. In vitro studies showed that L-FABP strongly bound glucose and glucose-1-phosphate (K(d) = 103 ± 19 nM and K(d) = 20 ± 3 nM, respectively), resulting in altered L-FABP conformation, increased affinity for lipid ligands, and enhanced interaction with PPARα. In living cells, glucose stimulated cellular uptake and nuclear localization of a nonmetabolizable fluorescent fatty acid analog (BODIPY C-16), particularly in the presence of L-FABP. These data suggest for the first time a direct role of glucose in facilitating L-FABP-mediated uptake and distribution of lipidic ligands to the nucleus for regulation of PPARα transcriptional activity.

The Role of the Placenta in Intrauterine Growth Restriction (IUGR)

Intrauterine growth restriction (IUGR) represents a reduction from the physiological growth rate. Fetal growth depends from the maternal supply of nutrients through the placenta into the umbilical circulation. Consequently, fetal growth restriction is associated with a reduced nutritional placental supply and this can result from a decrease in utero-placental blood flows as well as a reduced placental transport capacity. In IUGR, the placental supply of amino acids is significantly reduced independently from the severity of growth restriction and from the presence of hypoxia. Moreover, maternal-fetal gradients of glucose are increased in severe IUGR fetuses, i. e. those with alterations of umbilical blood flows, and reduced conversion ratios of long chain-polyunsaturated fatty acids (LC-PUFA) from their parent fatty acids have been demonstrated. Mouse and human models suggest that epigenetic regulation of fetal growth may also play a significant role, through placental imprinted genes. This review summarizes the current knowledge about placental role in intrauterine growth restriction.

Whole Blood Fatty Acid Composition Differs in Term Versus Mildly Preterm Infants: Small Versus Matched Appropriate for Gestational Age

To investigate the associations between whole blood fatty acid (FA) profile and restricted intrauterine growth, any small for gestational age (SGA) infant born in our maternity ward through 1 y was matched with two appropriate for gestational age (AGA), of the same GA +/- 0.5 wk, infants, further subdivided into term and preterm. Whole blood was collected at d 4 on a strip and FA % composition assessed by means of gas chromatography. The whole sample consisted of 28 SGA versus 56 AGA born at term and 20 SGA versus 40 AGA born preterm at around 35 wks. Parent FA of the n-6 and n-3 FA families were higher in preterm groups, whereas docosahexaenoic acid was higher in term AGA (median % values, 3.9 versus 3.7 in term SGA, 2.8 in preterm AGA, and 2.5 in preterm SGA, p < 0.001). Term AGA had markedly higher values for the docosahexaenoic acid/alpha-linolenic acid ratio (median value: 91, versus 18 in term SGA, 12 in preterm AGA, and 10 in preterm SGA, p < 0.001). Term SGA had significantly lower levels of total monounsaturated FA and higher levels of eicosapentaenoic acid. Therefore, the 4-d whole blood FA pattern is associated with both GA and birth weight.

Fishing for brain power?

The long chain polyunsaturated fatty acids (LCPUFA) arachidonic acid and docosahexaenoic acid (DHA) are predominant in the central nervous system. Neuronal synapses and photoreceptors in the retina are particularly rich...

Chemical C2-elongation of polyunsaturated fatty acids

Three fatty acids were synthesized from commercially available α-linolenic, stearidonic and eicosapentaenoic acids by C2-elongation using a four step preparative technique. The parent fatty acid methyl esters were reduced to alcohols with LiAlH 4, converted to bromides by treatment with triphenylphosphine dibromide, coupled with a lithiated C2-elongation block – 2,4,4-trimethyl-2-oxazoline – to form the corresponding 2,2-dimethyloxazolines of C2-elongated fatty acids, and finally, converted to the target polyunsaturated fatty acids by acidic alcoholysis. Yields of more than 60% were achieved on a gram scale. The resulting 11Z,14Z,17Z-eicosatrienoic, 8Z,11Z,14Z,17Z-eicosatetraenoic and 7Z,10Z,13Z,16Z,19Z-docosapentaenoic acids were obtained as colorless oils with >98% purity and could be used for biochemical investigations without additional purification. The elongated fatty acids were free of byproducts that could result from Z-E isomerization or migration of double bonds.

Induction of Micronuclei in Human TK6 Lymphoblasts by 2‐Dodecylcyclobutanone, a Unique Radiolytic Product of Palmitic Acid

ABSTRACT: Palmitic acid, the most abundant fatty acid in the human diet, causes oxidative DNA damage, DNA strand breakage, necrosis, and apoptosis in human and rodent cells in vitro, while excess fatty acids in the diet increase the risk of colon cancer in vivo. Irradiation of palmitic acid leads to the formation of 2‐dodecylcyclobutanone (2‐DCB), a unique radiolytic product formed at part‐per‐million levels in fats. Recent research has raised the possibility that, like palmitic acid, 2‐DCB can also cause DNA strand breaks in human and rodent cells. In order to more fully understand the clastogenic potential of 2‐DCB, it was tested for the ability to induce the formation of micronuclei (MN) in human TK6 lymphoblasts. TK6 lymphoblasts were exposed to 13.3, 26.5, and 53 μM of 2‐DCB for 24 h, both with and without exogenous metabolic activation (EMA). The number of MN per 1000 binucleated cells was induced 2.65‐fold without EMA, and 2.85‐fold in the presence of EMA at the highest 2‐DCB concentration of 53 μM. Cytotoxicity of the TK6 lymphoblasts treated with 53 μM 2‐DCB was 51.7% in the absence of EMA, and 61.7% in the presence of EMA. Thus, like palmitic acid, 2‐DCB may be weakly clastogenic against human cells in vitro. Given the amount of 2‐DCB that would be consumed when compared with that of its clastogenic parent fatty acid, 2‐DCB is unlikely to have any significant impact on human health.

Essential fatty acids and mental illness

SummaryThe treatment of psychiatric illness requires novel pharmacological strategies. There is a growing body of evidence examining the role of neuronal phospholipid abnormalities in the pathogenesis of psychiatric illness, particularly in schizophrenia. However, work in other conditions like mood disorders are also showing interesting outcomes with EPA supplementation. Diseases that are considered to have a genetic basis may be significantly influenced by environmental factors including dietary supplementation. The suggestion that EFA supplementation may prevent the onset of symptoms of a psychiatric disease or aberrant behaviour needs longitudinal randomized controlled research. In recent years the focus has shifted from omega-6 to omega-3. It is true that western diets have far more omega-6 than omega-3. In the 1980s, there were positive outcomes in research studies using GLA in schizophrenia (Vaddadi et al., ). Future research needs to incorporate studies using pure GLA. Research should not be restricted to parent fatty acid (omega-3) supplementation alone but be expanded to include bioactive down-the-chain metabolites. The recent identification of novel omega-3 derived mediators such as resolvins and neuroprotectins, which are a highly bioactive (1–10 nMol range), may well have some role to play in psychiatric disorders; however this remains highly speculative at this stage.

The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina

In this work we advance the hypothesis that omega-3 (omega-3) long-chain polyunsaturated fatty acids (LCPUFAs) exhibit cytoprotective and cytotherapeutic actions contributing to a number of anti-angiogenic and neuroprotective mechanisms within the retina. omega-3 LCPUFAs may modulate metabolic processes and attenuate effects of environmental exposures that activate molecules implicated in pathogenesis of vasoproliferative and neurodegenerative retinal diseases. These processes and exposures include ischemia, chronic light exposure, oxidative stress, inflammation, cellular signaling mechanisms, and aging. A number of bioactive molecules within the retina affect, and are effected by such conditions. These molecules operate within complex systems and include compounds classified as eicosanoids, angiogenic factors, matrix metalloproteinases, reactive oxygen species, cyclic nucleotides, neurotransmitters and neuromodulators, pro-inflammatory and immunoregulatory cytokines, and inflammatory phospholipids. We discuss the relationship of LCPUFAs with these bioactivators and bioactive compounds in the context of three blinding retinal diseases of public health significance that exhibit both vascular and neural pathology. How is omega-3 LCPUFA status related to retinal structure and function? Docosahexaenoic acid (DHA), a major dietary omega-3 LCPUFA, is also a major structural lipid of retinal photoreceptor outer segment membranes. Biophysical and biochemical properties of DHA may affect photoreceptor membrane function by altering permeability, fluidity, thickness, and lipid phase properties. Tissue DHA status affects retinal cell signaling mechanisms involved in phototransduction. DHA may operate in signaling cascades to enhance activation of membrane-bound retinal proteins and may also be involved in rhodopsin regeneration. Tissue DHA insufficiency is associated with alterations in retinal function. Visual processing deficits have been ameliorated with DHA supplementation in some cases. What evidence exists to suggest that LCPUFAs modulate factors and processes implicated in diseases of the vascular and neural retina? Tissue status of LCPUFAs is modifiable by and dependent upon dietary intake. Certain LCPUFAs are selectively accreted and efficiently conserved within the neural retina. On the most basic level, omega-3 LCPUFAs influence retinal cell gene expression, cellular differentiation, and cellular survival. DHA activates a number of nuclear hormone receptors that operate as transcription factors for molecules that modulate reduction-oxidation-sensitive and proinflammatory genes; these include the peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and the retinoid X receptor. In the case of PPAR-alpha, this action is thought to prevent endothelial cell dysfunction and vascular remodeling through inhibition of: vascular smooth muscle cell proliferation, inducible nitric oxide synthase production, interleukin-1 induced cyclooxygenase (COX)-2 production, and thrombin-induced endothelin 1 production. Research on model systems demonstrates that omega-3 LCPUFAs also have the capacity to affect production and activation of angiogenic growth factors, arachidonic acid (AA)-based vasoregulatory eicosanoids, and MMPs. Eicosapentaenoic acid (EPA), a substrate for DHA, is the parent fatty acid for a family of eicosanoids that have the potential to affect AA-derived eicosanoids implicated in abnormal retinal neovascularization, vascular permeability, and inflammation. EPA depresses vascular endothelial growth factor (VEGF)-specific tyrosine kinase receptor activation and expression. VEGF plays an essential role in induction of: endothelial cell migration and proliferation, microvascular permeability, endothelial cell release of metalloproteinases and interstitial collagenases, and endothelial cell tube formation. The mechanism of VEGF receptor down-regulation is believed to occur at the tyrosine kinase nuclear factor-kappa B (NFkappaB). NFkappaB is a nuclear transcription factor that up-regulates COX-2 expression, intracellular adhesion molecule, thrombin, and nitric oxide synthase. All four factors are associated with vascular instability. COX-2 drives conversion of AA to a number angiogenic and proinflammatory eicosanoids. Our general conclusion is that there is consistent evidence to suggest that omega-3 LCPUFAs may act in a protective role against ischemia-, light-, oxygen-, inflammatory-, and age-associated pathology of the vascular and neural retina.

Clinical prevention of sudden cardiac death by n-3 polyunsaturated fatty acids and mechanism of prevention of arrhythmias by n-3 fish oils.

This review will be limited specifically to the beneficial prevention by the n-3 polyunsaturated fatty acids (PUFAs) of arrhythmic deaths, including sudden cardiac death, which annually causes some 300 000 deaths in the United States and millions more worldwide. We will also show that the growing body of positive clinical studies is supported by what has been learned in animal and laboratory studies regarding the mechanism by which n-3 PUFAs prevent cardiac arrhythmias. See p 2632 Figure 1 shows the 2 essential classes of PUFAs, the n-6 (ω6) and n-3 (ω3) classes. Both classes are “essential” because we cannot make them in our bodies. They must come in our diets, and they are essential for normal growth, development, and optimal function of brain, heart, and probably other systems. The parent fatty acid of the n-6 class, linoleic acid (C18:2n-6; LA) has 18 carbon atoms in its acyl chain, and the first C=C double bond is 6 carbons back from the methyl end of the fatty acid, hence the “n-6” appellation. In the bodies of animals, including humans, LA can be elongated and desaturated through a series of enzymatic steps to form arachidonic acid (C20:4n-6; AA). AA is the source of the n-6 eicosanoids that result from oxygenation of AA by cyclooxygenase, lipoxygenase, and epoxygenase enzymes to form prostaglandins, leukotrienes, lipoxines, and P-450 compounds, which in many instances are potent cell messengers. Figure 1. Two classes of essential PUFAs. In the chloroplast of green plants, algae, and phytoplankton, LA can be further desaturated in the n-3 position to yield α-linolenic acid (C18:3 n-3; ALA), the 18-carbon parent fatty acid of the n-3 class. ALA can be further elongated and desaturated by the same enzymes that convert n-6 LA to AA to form the 20-carbon n-3 analog of AA, namely, eicosapentaenoic acid …

EPR spin-trapping evidence for the direct, one-electron reduction of tert-butylhydroperoxide to the tert-butoxyl radical by copper(II): paradigm for a previously overlooked reaction in the initiation of lipid peroxidation.

Lipid peroxidation is often initiated using Cu(II) ions. It is widely assumed that Cu(II) oxidizes preformed lipid hydroperoxides to peroxyl radicals, which propagate oxidation of the parent fatty acid via hydrogen atom abstraction. However, the oxidation of alkyl hydroperoxides by Cu(II) is thermodynamically unfavorable. An alternative means by which Cu(II) ions could initiate lipid peroxidation is by their one-electron reduction of lipid hydroperoxides to alkoxyl radicals, which would be accompanied by the generation of Cu(III). We have investigated by EPR spectroscopy, in conjunction with the spin trap 5,5-dimethyl-1-pyrroline N-oxide, the reactions of various Cu(II) chelates with tert-butylhydroperoxide. Spectra contained signals from the tert-butoxyl, methyl, and methoxyl radical adducts. In many previous studies, the signal from the methoxyl adduct has been assigned incorrectly to the tert-butylperoxyl adduct, which is now known to be unstable, releasing the tert-butoxyl radical upon decomposition. This either is trapped by 5,5-dimethyl-1-pyrroline N-oxide or undergoes beta-scission to the methyl radical, which either is trapped or reacts with molecular oxygen to give, ultimately, the methoxyl radical adduct. By using metal chelates that are known to be specific in either their oxidation or reduction of tert-butylhydroperoxide (the Cu(II) complex of bathocuproine disulfonic acid and the Fe(II) complex of diethylenetriaminepentaacetic acid, respectively) for comparison, we have been able to deduce, from the relative concentrations of the three radical adducts, that the Cu(II) complexes tested each reduce tert-butylhydroperoxide directly to the tert-butoxyl radical. These findings suggest that a previously overlooked reaction, namely the direct reduction of preformed lipid hydroperoxides to alkoxyl radicals by Cu(II), may be responsible for the initiation of lipid peroxidation by Cu(II) ions.

A procedure for preparing oxazolines of highly unsaturated fatty acids to determine double bond positions by mass spectrometry

A convenient, mild, reliable method has been developed for preparing oxazolines of fatty acids and for using these derivatives to determine double bond locations in long-chain polyunsaturated and polyconjugated fatty acids. Fatty acyl mixed anhydrides are prepared using isobutylchloroformate and then converted to their ethanolamides by treatment with ethanolamine. Ethanolamides are subsequently cyclized to the corresponding oxazolines in >or=85% yields by treatment with trifluoroacetic anhydride under mild conditions (>50 degrees for 30-60 min). This general protocol can also be used to synthesize 4,4-dimethyloxazoline and benzoxazole derivatives of fatty acids. Gas chromatography-mass spectrometry of oxazoline derivatives of fatty acids yields prominent ions diagnostic of the structures of the parent fatty acids and, in the case of unsaturated fatty acids, indicating the positions of the double bonds. The utility of the method is illustrated with several fatty acids, including the conjugated 4E,6E,8E,10E,13Z,16Z,19Z-docosaheptaenoic acid.

The potential benefits of using fish oil in relation to preterm labor: the case for a randomized controlled trial?

The potential benefits of using fish oil in relation to preterm labor: the case for a randomized controlled trial?

Omega-6/omega-3 ratio and brain-related functions.

While the general public typically perceives lipids and fats as ‘harmful’ components of the diet (as in the popular slogan: ‘fat kills’), the scientific story is in fact very different. Among the major scientific research efforts of the recent period, in the area of neuroscience, we find the recognition of the ‘essential fatty acids’ (EFA). The profound effects of various fatty acids, and equally profound effects of their deficits, are appreciated by a variety of disciplines, including (but not necessarily limited to) lipid biochemistry, physiology, nutrition, psychology, psychiatry, and neurosciences at large. Recently, the issue of lipids, and fatty acids ratio in diets, became an important issue. Simopoulos [1] showed the historical shift from a ‘balanced’ omega–6 and omega–3 ratio diet, towards a marked and significant reduction in the omega–3 intake, and explained that the general ‘Western diet’ of today can in actual fact be considered an omega–3deficient diet. Her concern is that this ‘deficiency’ may lead to coronary heart disease and high cancer mortality. Linoleic acid (LA; omega–6; 6; 18:26) is the parent fatty acid of the omega–6 group. Linoleic acid must be supplied to the body by the diet, because the body is unable to synthesize it. All other members of the omega–6 group are derivatives of LA. Similarly, the parent compound of the omega–3 group is alpha-linolenic acid (ALA, omega–3, 3, 18:33). All other members of the omega–3 group are merely derivatives of ALA, and together they form the polyunsaturated fatty acids (PUFA). In each group, the derivatives can convert to longer chain fatty acids by using two mechanisms: desaturation and elongation.

Macronutrient innovations: The role of fats and sterols in human health

Dietary intake of fats and sterols has long been known to play a critical role in human health. High proportions of saturated fat, which increase blood cholesterol levels, are mainly found in animal fat and some plant oil (e.g. cocoa butter, palm oil etc.). The predominant polyunsaturated fatty acid (PUFA) in the Western diet is linoleic acid (LA; 18:2n‐6), an essential fatty acid, which is commonly found in vegetable seed oils. This is the parent fatty acid of n‐6 series PUFA, which can be converted in vivo to C20 and C22 n‐6 long chain (LC) PUFA. α‐linolenic acid (ALA; 18:3n‐3) is less abundant than LA and is another essential fatty acid; ALA is also present in some vegetable oils such as perilla, flaxseed, canola, soybean and walnut oils, and is the precursor of C20 and C22 n‐3 LC PUFA. Sterols are widely distributed in animal tissue and plants, with cholesterol being the major sterol in animal tissue and β‐sitosterol, campesterol and stigmasterol being the main sterols in plants. It has long been recognized that an increased dietary intake of saturated fat and (to a lesser extent) cholesterol, raises plasma/serum total and low‐density lipoprotein (LDL)‐cholesterol, and PUFA decreases these levels. Results from recent studies have shown that plasma/serum levels of lipids and lipoprotein lipids can also be decreased by plant sterols (phytosterols) and diacylglycerol (DAG). Conjugated linoleic acid (CLA, cis‐9,trans‐11−18:2) has been reported to have anticancer and antidiabetic activities. Fat as the DAG form has also been reported to have anti‐obesity effects. Omega‐3 PUFA have a beneficial effect on increased heart rate variability, decreased risk of stroke, reduction of both systolic and diastolic blood pressure and may be effective in managing depression in adults. Gamma‐linolenic acid (GLA) and phytosterols have an anti‐inflammatory activity. The GLA, when combined with docosahexaenoic acid (DHA), have been reported to have a beneficial effect in hyperactive children. These data show that various lipids are powerful bioactive compounds.

Dietary EPA reduces tumor load in ApcMin/+ mice by altering arachidonic acid metabolism, but conjugated linoleic acid, gamma--and alpha-linolenic acids have no effect.

Colorectal cancer is the second leading cause of cancer deaths in the United States and several lines of evidence implicate environmental factors, specifically dietary components, as major variables influencing colorectal cancer incidence. Among these, the amount and type of dietary fat consumed is of particular importance. Studies in humans and in animal models overwhelmingly indicate a protective effect of the (n-3) polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA, 20:5 (n-3)) and docosahexaenoic acid (DHA, 22:6 (n-3)) and the mechanism is largely thought to be related to interference with biosynthesis of 2-series prostaglandins from arachidonic acid (AA, 20:4 (n-6)). Compared to EPA and DHA, a-linolenic acid (ALA, 18:3 (n-3)), the parent fatty acid of the (n-3) family, conjugated linoleic acid (cLA, 18:2 (n-6) and (n-7))