Dietary trans α‐linolenic acid does not inhibit Δ5‐ and Δ6‐desaturation of linoleic acid in man

Dietary trans monoenes have been associated with an increased risk of heart disease in some studies and this has caused much concern. Trans polyenes are also present in the diet, for example, trans α‐linolenic acid is formed during the deodorisation of α‐linolenic acid‐rich oils such as rapeseed oil. One would expect the intake of trans α‐linolenic acid to be on the increase since the consumption of rapeseed oil in the western diet is increasing. There are no data on trans α‐linolenic acid consumption and its effects. We therefore carried out a comprehensive study to examine whether trans isomers of this polyunsaturated fatty acid increased the risk of coronary heart disease. Since inhibition of Δ6‐desaturase had also been linked to heart disease, the effect of trans α‐linolenic acid on the conversion of [U‐¹³C]‐labelled linoleic acid to dihomo‐γ‐linolenic and arachidonic acid was studied in 7 healthy men recruited from the staff and students of the University of Edinburgh. Thirty percent of the habitual fat was replaced using a trans ‘free’‐ or ‘high’ trans α‐linolenic acid fat. After at least 6 weeks on the experimental diets, the men received 3‐oleyl, 1,2‐[U‐¹³C]‐linoleyl glycerol (15 mg twice daily for ten days). The fatty acid composition of plasma phospholipids and the incorporation of ¹³C‐label into n‐6 fatty acids were determined at day 8, 9 and 10 and after a 6‐week washout period by gas chromatography‐combustion‐isotope ratio mass spectrometry. Trans α‐linolenic acid of plasma phospholipids increased from 0.04 ? 0.01 to 0.17 ? 0.02 and cis ? ‐linolenic acid decreased from 0.42 ? 0.07 to 0.29 ? 0.08 g/100 g of fatty acids on the high trans diet. The composition of the other plasma phospholipid fatty acids did not change. The enrichment of phosphatidyl ¹³C‐linoleic acid reached a plateau at day 10 and the average of the last 3 days did not differ between the low and high trans period. Both dihomo‐γ‐linolenic and arachidonic acid in phospholipids were enriched in ¹³C, both in absolute and relative terms (with respect to ¹³C‐linoleic acid). The enrichment was slightly and significantly higher during the high trans period (P<0.05). Our data suggest that a diet rich in trans α‐linolenic acid (0.6% of energy) does not inhibit the conversion of linoleic acid to dihomo‐γ‐linolenic and arachidonic acid in healthy middle‐aged men consuming a diet rich in linoleic acid.     

Lipase‐mediated hydrolysis of flax seed oil for selective enrichment of α‐linolenic acid

Polyunsaturated fatty acids (PUFA) are important ingredients of human diet because of their prominent role in the function of human brain, eye and kidney. α‐Linolenic acid (ALA), a C18, n‐3 PUFA is a precursor of long chain PUFA in humans. Commercial lipases of Candida rugosa, Pseudomonas cepacea, Pseudomonas fluorescens, and Rhizomucor miehei were used for hydrolysis of flax seed oil. Reversed phase high performance liquid chromatography followed by gas chromatography showed that the purified oil contained 12 triacylglycerols (TAGs) with differences in fatty acid compositions. Flax seed oil TAGs contained α‐linolenic acid (50%) as a major fatty acid while palmitic, oleic, linoleic made up rest of the portion. Among the four commercial lipases C. rugosa has preference for ALA, and that ALA was enriched in free fatty acids. C. rugosa lipase mediated hydrolysis of the TAGs resulted in a fatty acid mixture that was enriched in α‐linolenic to about 72% yield that could be further enriched to 80% yield by selective removal of saturated fatty acids by urea complexation. Such purified ALA can be used for preparation of ALA‐enriched glycerides. Practical applications : This methodology allows purifying ALA from fatty acid mixture obtained from flax seed oil by urea complexation.     

Pneumocandin Biosynthesis: Involvement of a trans‐Selective Proline Hydroxylase

Echinocandins are cyclic nonribosomal hexapeptides based mostly on nonproteinogenic amino acids and displaying strong antifungal activity. Despite previous studies on their biosynthesis by fungi, the origin of three amino acids, trans‐4‐ and trans‐3‐hydroxyproline, as well as trans‐3‐hydroxy‐4‐methylproline, is still unknown. Here we describe the identification, overexpression, and characterization of GloF, the first eukaryotic α‐ketoglutarate/Fe^II‐dependent proline hydroxylase from the pneumocandin biosynthesis cluster of the fungus Glarea lozoyensis ATCC 74030. In in vitro transformations with L ‐proline, GloF generates trans‐4‐ and trans‐3‐hydroxyproline simultaneously in a ratio of 8:1; the latter reaction was previously unknown for proline hydroxylase catalysis. trans‐4‐Methyl‐L ‐proline is converted into the corresponding trans‐3‐hydroxyproline. All three hydroxyprolines required for the biosynthesis of the echinocandins pneumocandins A₀ and B₀ in G. lozoyensis are thus provided by GloF. Sequence analyses revealed that GloF is not related to bacterial proline hydroxylases, and none of the putative proteins with high sequence similarity in the databases has been characterized so far.     

N‐3 fatty acids for human nutrition: stability considerations

Currently there is great interest in dietary n‐3 fatty acids to promote health. The food industry aims to produce food products enriched in α‐linolenic acid (Ln), eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) to reduce some of the physiological effects of linoleic acid (L), the major polyunsaturated fatty acid in our diet. However, the goal is hampered by the susceptibility of the n‐3 fatty acids to oxidation. As a result the sensory and nutritional quality of such foods deteriorates. Lipid scientists therefore have to find a way to stabilise these fatty acids. Innovative technologies to protect n‐3 polyunsaturates using antioxidants, adequate preparation, refining and packaging of the oil are needed. In this paper we review the inherent stability and the stabilisation of these nutritionally valuable polyunsaturated fatty acids.     

Biosynthesis of Oxylipins by Rhizoctonia solani with Allene Oxide and Oleate 8S,9S‐Diol Synthase Activities

Oxylipin biosynthesis by fungi is catalyzed by both the lipoxygenase (LOX) family and the linoleate diol synthase (LDS) family of the peroxidase‐cyclooxygenase superfamily. Rhizoctonia solani, a pathogenic fungus, infects staple crops such as potato and rice. The genome predicts three genes with 9–13 introns, which code for tentative dioxygenase (DOX)–cytochrome P450 fusion enzymes of the LDS family, and one gene, which might code for a 13‐LOX. The objective was to determine whether mycelia or nitrogen powder of mycelia oxidized unsaturated C₁₈ fatty acids to LDS‐ or LOX‐related metabolites. Mycelia converted 18:2n‐6 to 8R‐hydroxy‐9Z,12Z‐octadecadienoic acid and to an α‐ketol, 9S‐hydroxy‐10‐oxo‐12Z‐octadecenoic acid. In addition to these metabolites, nitrogen powder of mycelia oxidized 18:2n‐6 to 9S‐hydroperoxy‐10E, 12Z‐octadecadienoic, and 13S‐hydroperoxy‐9Z,11E‐octadecadienoic acids; the latter was likely formed by the predicted 13‐LOX. 18:1n‐9 was transformed into 8S‐hydroperoxy‐9Z‐octadecenoic and into 8S,9S‐dihydroxy‐10E‐octadecenoic acids, indicating the expression of 8,9‐diol synthase. The allene oxide, 9S(10)epoxy‐10,12Z‐octadecadienoic acid, is unstable and decomposes rapidly to the α‐ketol above, indicating biosynthesis by 9S‐DOX‐allene oxide synthase. This allene oxide and α‐ketol are also formed by potato stolons, which illustrates catalytic similarities between the plant host and fungal pathogen.     

Heterocycles as Nonclassical Bioisosteres of α‐Amino Acids

Bioisosterism of α‐amino acids is often accomplished by replacing the α‐carboxylate with one of the many known carboxylic acid bioisosteres. However, bioisosterism of the whole α‐amino acid moiety is accomplished with heterocyclic bioisosteres that often display an acidic function. In this Minireview, we summarized the reported heterocycles as nonclassical bioisosteres of α‐amino acids, which include quinoxaline‐2,4(1H)‐dione, quinoxaline‐2,3(1H)‐dione and quinolin‐2(1H)‐one, azagrevellin and azepine‐derived structures. The binding mode of the crystalized bioisosteres were compared with those of the crystalized α‐amino acids that bind in the same domain, and where no data on the crystal structure were available, the displacement studies of known orthosteric ligands were used. The reported bioisosteres share the following essential structural features for mimicking α‐amino acids: an aromatic ring system joined to a lactam ring system with an acidic feature next to the lactam carbonyl, where this acidic feature together with the lactam carbonyl can mimic the α‐carboxylate, and the lactam nitrogen together with the aromatic ring system can mimic the α‐ammonium. The majority of these heterocycles can be prepared from three common corresponding starting materials: the corresponding anilines, isatins or anthranilic esters. The data collected here show the potential of this class of bioisosteres in the design of glutamate receptor ligands and beyond.     

Alpha‐Linolenic Acid,but Not Palmitic Acid,Negatively Impacts Survival,Asexual Reproductive Rate,and Clonal Offspring Size in Hydra oligactis

Hydra, as sit‐and‐wait predators with limited food selectivity, could serve as model organisms for the analysis of the effect of a particular dietary component on growth and reproduction. We investigated the effect of food quality and of diets enriched with palmitic (PAM) or α‐linolenic acid (ALA) on the life history traits of two hydra species: Hydra oligactis and Hydra vulgaris. We tested the hypothesis that a diet enriched with polyunsaturated fatty acids (PUFA) can stimulate growth and reproduction in simple metazoans with a sit‐and‐wait type of predatory strategy. Our results revealed that a diet based on Artemia nauplii, which are not a natural food for freshwater hydra, stimulated growth, asexual reproduction, and survival in hydra. Artemia nauplii were characterized by the highest lipid content of all used food sources. The analysis of the fatty acid content of hydra indicated the domination the n‐6 fatty acids over n‐3 (eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA], and ALA). Arachidonic acid appeared to be the dominant PUFA in Hydra, irrespective of diet supplementation with palmitic acid or ALA. The dietary supplementation of ALA negatively affected the survival, asexual reproductive rate, and size of clonal offspring of H. oligactis and had no effect on the life history traits of H. vulgaris. Our results also suggest that the hydras are not able to efficiently convert ALA into other essential fatty acids, such as EPA and DHA. To our knowledge, this is the first report about the adverse effects of n‐3 fatty acid supplementation in primitive metazoans such as hydra.     

Enzymatic Synthesis of Enantiopure α‐ and β‐Amino Acids by Phenylalanine Aminomutase‐Catalysed Amination of Cinnamic Acid Derivatives

The phenylalanine aminomutase (PAM) from Taxus chinensis catalyses the conversion of α‐phenylalanine to β‐phenylalanine, an important step in the biosynthesis of the N‐benzoyl phenylisoserinoyl side‐chain of the anticancer drug taxol. Mechanistic studies on PAM have suggested that (E)‐cinnamic acid is an intermediate in the mutase reaction and that it can be released from the enzyme's active site. Here we describe a novel synthetic strategy that is based on the finding that ring‐substituted (E)‐cinnamic acids can serve as a substrate in PAM‐catalysed ammonia addition reactions for the biocatalytic production of several important β‐amino acids. The enzyme has a broad substrate range and a high enantioselectivity with cinnamic acid derivatives; this allows the synthesis of several non‐natural aromatic α‐ and β‐amino acids in excellent enantiomeric excess (ee >99 %). The internal 5‐methylene‐3,5‐dihydroimidazol‐4‐one (MIO) cofactor is essential for the PAM‐catalysed amination reactions. The regioselectivity of amination reactions was influenced by the nature of the ring substituent.     

α‐, γ‐ and δ‐ Tocopherols as inhibitors of isomerization and decomposition of cis,trans methyl linoleate hydroperoxides

The effects of α‐, γ‐ and δ‐tocopherols on the stability and decomposition reactions of lipid hydroperoxides were studied. Isomerization and decomposition of cis,trans methyl linoleate hydroperoxides (cis,trans ML‐OOH) in hexadecane at 40 °C were followed by high‐performance liquid chromatography. Due to its higher hydrogen donating ability, α‐tocopherol was more efficient than γ‐ and δ‐tocopherols in inhibiting the isomerization of cis,trans ML‐OOH to trans,trans ML‐OOH. α‐Tocopherol stabilized hydroperoxides into the cis,trans configuration, whereas γ‐ and δ‐tocopherols allowed hydroperoxides to convert into trans,trans isomers. Thus, the biological importance of α‐tocopherol as compared to other tocopherols may be partly due to its better efficacy in protecting the cis,trans configuration of hydroperoxides formed, for example, in the enzymatic oxidation of polyunsaturated fatty acids. The isomeric configuration of hydroperoxides has an impact on biological activities of further oxidation products of polyunsaturated fatty acids. Paradoxically, the order of activity of tocopherols with regard to hydroperoxide decomposition was different from that obtained for hydroperoxide isomerization. γ‐ and δ‐tocopherols were more efficient inhibitors of ML‐OOH decomposition when compared to α‐tocopherol. A loss of antioxidant efficiency, observed as the tocopherol concentration increased from 2 to 20 mM, was highest for α‐tocopherol but was also evident for γ‐ and δ‐tocopherols. Thus, the differences in the relative effects of tocopherols at differing concentrations seem to result from a compromise between their radical scavenging efficiency and participation in side reactions of peroxidizing nature.     

Multi‐Enzymatic Synthesis of Optically Pure β‐Hydroxy α‐Amino Acids

A novel enzymatic production system of optically pure β‐hydroxy α‐amino acids was developed. Two enzymes were used for the system: an N‐succinyl L ‐amino acid β‐hydroxylase (SadA) belonging to the iron(II)/α‐ketoglutarate‐dependent dioxygenase superfamily and an N‐succinyl L ‐amino acid desuccinylase (LasA). The genes encoding the two enzymes are part of a gene set responsible for the biosynthesis of peptidyl compounds found in the Burkholderia ambifaria AMMD genome. SadA stereoselectively hydroxylated several N‐succinyl aliphatic L ‐amino acids and produced N‐succinyl β‐hydroxy L ‐amino acids, such as N‐succinyl‐L ‐β‐hydroxyvaline, N‐succinyl‐L ‐threonine, (2S,3R)‐N‐succinyl‐L ‐β‐hydroxyisoleucine, and N‐succinyl‐L ‐threo‐β‐hydroxyleucine. LasA catalyzed the desuccinylation of various N‐succinyl‐L ‐amino acids. Surprisingly, LasA is the first amide bond‐forming enzyme belonging to the amidohydrolase superfamily, and has succinylation activity towards the amino group of L ‐leucine. By combining SadA and LasA in a preparative scale production using N‐succinyl‐L ‐leucine as substrate, 2.3 mmol of L ‐threo‐β‐hydroxyleucine were successfully produced with 93% conversion and over 99% of diastereomeric excess. Consequently, the new production system described in this study has advantages in optical purity and reaction efficiency for application in the mass production of several β‐hydroxy α‐amino acids.

     

The impact of dietary mono‐ and poly‐unsaturated fatty acids on risk factors for atherosclerosis in humans

The fatty acid composition of the diet has various effects on atherosclerosis risk factors. Dietary saturated fatty acids (SFA) and trans‐unsaturated fatty acids increase the low‐density lipoprotein (LDL)‐/high‐density lipoprotein (HDL)‐cholesterol ratio in serum, while these fats do not have a significant bearing on serum triglyceride levels. By contrast, dietary monounsaturated fatty acids (MUFA), n‐6 polyunsaturated fatty acids (PUFA), and α‐linolenic acid (C18:3n‐3) similarly reduce LDL cholesterol concentrations, while their influence on serum HDL cholesterol and triglycerides is not appreciable. Dietary long‐chain n‐3 PUFA slightly increase serum LDL cholesterol concentrations, but are nevertheless considered salubrious with regard to serum lipids due to the distinct triglyceride‐lowering effects. MUFA‐rich compared to n‐6 PUFA‐rich diets strongly reduce the in vitro oxidizability of LDL. The available studies on this subject also suggest that n‐3 PUFA in the small amounts usually present in the diet are not unduly harmful. These findings are consistent with reports from observational studies: the amount of SFA is positively and the amount of MUFA and n‐6 PUFA in the diet is inversely associated with the risk of cardiovascular disease in most epidemiological studies. The available studies have had an impact on current dietary guidelines, which unanimously recommend that most of the dietary fat should be in the form of MUFA, while the amount of SFA and trans fatty acids in the diet should be as low as possible.     

Evidence of Strict Stereospecificity in the Structure of sn‐1,2‐Diacyl‐3‐Acetyl‐Glycerols from Euonymus maximowiczianus Seeds Using Nuclear Magnetic Resonance Spectroscopy

Asymmetric, optically active sn‐1,2‐diacyl‐3‐acetyl‐glycerols (AcDAG) have been known to scientists for several decades. However, to date, the problem of their structure has not been definitely resolved, which has led to a vast diversity of terms used for their designation in the literature. Using two‐dimensional nuclear magnetic resonance, we have investigated AcDAG from the mature seeds of Euonymus maximowiczianus, from which we have been able to both identify a correlation of the methyl group in acetic acid residue with protons at the carbon atom at sn‐3 position in the glycerol residue of the AcDAG molecule and, for the first time, demonstrate that this correlation is observed exclusively with one carbon atom at the α‐position, but not with two as would have been expected in case of a racemic mixture. Moreover, results of our analysis of AcDAG isolated from the seeds of E. maximowiczianus directly confirm that diacylglycerol‐3‐acetyl‐transferase is responsible for their biosynthesis, which reveals a strict specificity not only to acetyl‐CoA as one of the substrates but also to the sn‐3‐position of the glycerol residue in sn‐1,2‐diacylglycerol during their biosynthesis.     

Plant sn‐Glycerol‐3‐Phosphate Acyltransferases: Biocatalysts Involved in the Biosynthesis of Intracellular and Extracellular Lipids

Acyl‐lipids such as intracellular phospholipids, galactolipids, sphingolipids, and surface lipids play a crucial role in plant cells by serving as major components of cellular membranes, seed storage oils, and extracellular lipids such as cutin and suberin. Plant lipids are also widely used to make food, renewable biomaterials, and fuels. As such, enormous efforts have been made to uncover the specific roles of different genes and enzymes involved in lipid biosynthetic pathways over the last few decades. sn‐Glycerol‐3‐phosphate acyltransferases (GPAT) are a group of important enzymes catalyzing the acylation of sn‐glycerol‐3‐phosphate at the sn‐1 or sn‐2 position to produce lysophosphatidic acids. This reaction constitutes the first step of storage‐lipid assembly and is also important in polar‐ and extracellular‐lipid biosynthesis. Ten GPAT have been identified in Arabidopsis, and many homologs have also been reported in other plant species. These enzymes differentially localize to plastids, mitochondria, and the endoplasmic reticulum, where they have different biological functions, resulting in distinct metabolic fate(s) for lysophosphatidic acid. Although studies in recent years have led to new discoveries about plant GPAT, many gaps still exist in our understanding of this group of enzymes. In this article, we highlight current biochemical and molecular knowledge regarding plant GPAT, and also discuss deficiencies in our understanding of their functions in the context of plant acyl‐lipid biosynthesis.     

Genetic Improvement of the Fatty Acid Biosynthesis System to Alter the ω-6/ω-3 Ratio in the Soybean Seed

A high ω‐6/ω‐3 fatty acid ratio in the soybean seed adversely affects human health. The objective of the present study was to improve the fatty acid biosynthesis to reduce the ω‐6/ω‐3 ratio by combining the FAD2‐1A and FAD2‐1B mutant alleles with α‐linolenic acid (ω‐3) related alleles from wild soybean. The F₂ population comprising 2320 F_2:3 lines developed from S08‐14717 × PI 483463 cross exhibited significant variation for fatty acid components. Of these, 114 lines were advanced to the F_5:6 generation and genotyped for FAD2‐1A and FAD2‐1B alleles. The lines carrying mutant FAD2‐1A and FAD2‐1B alleles showed ~ 761 g kg^?1 oleic, and ~ 50 g kg^?1 linoleic acids, which reduced ω‐6/ω‐3 ratios to ~ 0.6. Conversely, the lines carrying FAD2‐1A or FAD2‐1B mutant alleles had 267 or 399 g kg^?1 oleic, 327 or 471 g kg^?1 linoleic, and 120 or 130 g kg^?1 α‐linolenic acids concentration, respectively. The elevated α‐linolenic acid resulted in the reduction of ω‐6/ω‐3 ratios in the range 2.5–3.9. The present study demonstrated that combining FAD2 mutant alleles with α‐linolenic acid‐related alleles from wild soybean reduces the seed ω‐6/ω‐3 ratio.     

Divergent Response of Murine and Porcine Adipocytes to Stimulation of Browning Genes by 18‐Carbon Polyunsaturated Fatty Acids and Beta‐Receptor Agonists

Long‐chain fatty acids (LCFA) are known to activate brown and beige adipocytes. However, very little is known about the effects of the number and the position of double bonds in LCFA with the same length on brown fat‐specific gene expression. To determine the specificity of LCFA in the regulation of these genes in different adipocyte models, fully differentiated 10T1/2, 3T3‐L1, murine, or porcine primary adipocytes (obtained from the subcutaneous fat pad of C57BL/6 mice or Landrace × Yorkshire × Duroc crossbred piglets) were treated with 50 μM of the following 18‐carbon fatty acids: stearic acid (STA; 18:0), oleic acid (OLA; 18:1, Δ9), linoleic acid (LNA; 18:2, Δ9,12), α‐linolenic acid (ALA; 18:3, Δ9,12,15), γ‐linolenic acid (GLA; 18:3, Δ6,9,12), or pinolenic acid (PLA; 18:3, Δ5,9,12) for 24 h with or without 4‐h norepinephrine (NE) treatment. Expression levels of thermoregulatory markers were measured by quantitative real‐time PCR. LNA, ALA, GLA, and PLA upregulated Ucp1 expression and tended to upregulate Pgc1a expression in murine primary adipocytes, but not in 10T1/2, 3T3‐L1, and porcine primary adipocytes. In murine primary adipocytes, NE induced a higher expression of Ucp1 and Pgc1a than non‐NE‐treated cells, and PLA augmented the NE effect. In 10T1/2 cells, NE upregulated Ucp1 and Pgc1a expression, but there was no fatty acid effect. However, 3T3‐L1 cells were insensitive to both fatty acid and beta‐adrenergic agonist stimulation. These results indicate that different adipocyte cell types have different levels of sensitivity to both LCFA and beta agonists in regard to induction of brown fat‐specific gene expression.     

2-Hydroxyhexadecanoic and 8,9,13-trihydroxydocosanoic acid accumulation by yeasts treated with fumonisin B1

Fumonisin B₁ is a sphingolipid-like compound that enhances the accumulation of yeast sphingolipids and 2-hydroxy fatty acids. These lipids occur both as freely extractable and cell bound components in yeast fermentations. Both free and bound 2-hydroxy fatty acids produced byPichia sydowiorum NRRL Y-7130 were increased when fumonisin B₁ (50 mg/L) was added to the usual growth medium containing yeast extract/malt extract/peptone/glucose. Fumonisin-treated cultures contained 38 mg/L more 2-hydroxyhexadecanoic and 15 mg/L more 2-hydroxyoctadecanoic acids than did untreated cultures. By contrast, fumonisin inhibited the accumulation of free 8,9,13-trihydroxydocosanoic acid inRhodotorula sp. YB-2501 cultures, leading to 240 mg/L lower trihydroxy acid production than by untreated cultures.     

Palladium‐Catalyzed Decarboxylative Acylation of O‐Phenyl Carbamates with α‐Oxocarboxylic Acids at Room Temperature

A palladium‐catalyzed oxidative acylation of O‐phenyl carbamates with α‐oxocarboxylic acids via selective aromatic C H bond activation is described. This protocol represents the first ortho‐acylation of phenol derivatives, and a catalytic amount of triflic acid additive is crucial for this transformation.     

Nutritional value of rapeseed oil and its high oleic/low linolenic variety – A call for differentiation

To offer the best choice of healthy and acceptable food to the consumer a coordination of plant breeding, food processing and nutrition science is required. Here the nutritional aspects of the high oleic/low linolenic (HOLLi) varieties of rapeseed with a low α‐linolenic acid content of about 3% are reviewed. The content of α‐linolenic acid amounting to around 9% is the hallmark of the positive nutritional value of the original (erucic acid free) 00 varieties of rapeseed oil (“canola” quality in North America). n‐3 fatty acids are endowed with the property to protect the cardiovascular system from chronic disease and the consumption of food containing n‐3 fatty acids is explicitly recommended by national and international nutritional and medical authorities. Although the use of HOLLi with a low n‐3 fatty acid content can be unavoidable for specific purposes, because of technological and health considerations the continuous future consumption of the original rapeseed oil with around 9% of α‐linolenic acid by the consumer should have high priority from the standpoint of public health. To pursue this aim confusion of the consumer must be avoided by creating a new name and a new brand for HOLLi varieties.     

Branched‐chain fatty acids as activators of peroxisome proliferator‐activated receptors

We observed earlier that phytanic acid activated subtype α of the peroxisome proliferator‐activated receptor (PPAR) via the cytosolic liver‐type fatty acid‐binding protein (L‐FABP). In a further search for minor lipid nutrients that interact with genes, we explored here the potential of branched‐chain fatty acids to serve as agonists for the PPAR subtypes α, β and γ in rodent and human molecular test systems. Beyond chlorophyll‐derived pristanic and phytanic acids, bacteria‐derived iso‐ and anteiso‐fatty acids and avian‐derived ‘uropygial’ fatty acids were tested by transactivation assay. In addition, we studied binding of these fatty acids to recombinantly expressed PPAR ligand binding domains (LBDs) and to L‐FABP by competition with fluorescent parinaric acid. In contrast to single methyl‐branched agonists, multi methyl‐branched fatty acids had high transactivation potentials in either test system; in addition, some agonists of the latter were highly subtype selective. Multi methyl‐branched chain fatty acids were superior activators of human PPARγ, a preference not seen in the murine test system. High‐affinity binding of isoprenoid‐derived pristanic and phytanic acids to PPARγ‐LBD and to L‐FABP was observed, and also of pristanic acid to PPARα‐LBD. Polyketidic uropygial fatty acids bound to PPARγ‐LBD only, though weakly. As both isoprenoid and polyketidic fatty acids showed high activation potentials, it became clear that binding data determined in vitro cannot predict biological activity as determined by transactivation assay. For pristanic acid, however, a signalling path similar to that found for phytanic acid can be concluded. Taken together, multi methyl‐branched fatty acids of the human food chain can affect cellular metabolism through regulating gene expression.