Comparison of catabolic rates of fatty acids using stable isotope and isotope‐ratio mass spectrometry

The catabolic rates of individual fatty acids in mice were compared using stable isotope (¹³C)‐labeled fatty acids and isotope‐ratio mass spectrometry (IRMS). The catabolic rates were evaluated from the ratio of ¹³C and ¹²C in carbon dioxide expired by mice. The results showed that the catabolic rate of octanoic acid is three times faster than that of palmitic acid. This result is consistent with previous reports using radioisotope ¹⁴C showing that medium‐chain fatty acids are more easily beta‐oxidized than long‐chain fatty acids. The catabolic rates of odd‐numbered fatty acids such as pentadecanoic acid and heptadecanoic acid were significantly lower compared to those of even‐numbered fatty acids such as palmitic acid. These findings support previous reports that show odd‐numbered fatty acids easily accumulating in body fat. The high accumulation of odd‐numbered fatty acids in body fat thus directly reflects a low degree of beta‐oxidization. The combination of stable isotope‐labeled compounds and IRMS serves as a powerful tool in lipid analysis.     

Hepatic metabolism of 1-14C octanoic and 1-14C palmitic acids

The hepatic metabolism of 1⁻¹⁴C octanoic acid was compared with that of 1⁻¹⁴C palmitic acid in male rats which were fed. After intraportal injection only 1/6 to 1/18 as much octanoic acid as palmitic acid was incorporated into hepatic lipids. In contrast, octanoic acid yielded two to four times as much water-soluble product as did palmitic acid. Similar, but even more impressive, differences between the incorporation of these fatty acids into hepatic lipids were observed in liver slices incubated with¹⁴C octanoate and¹⁴C palmitate. The oxidation of octanoate to CO₂ was more than 10 times as great as that of palmitate. With both substrates, triglycerides comprised almost half the labeled lipid recovered. However octanoate yielded a higher proportion of labeled, unesterified fatty acids and a lower proportion of labeled phospholipid and monoglycerides than did palmitate. Most of the¹⁴C recovered in hepatic lipids after incubation with 1⁻¹⁴C octanoate was found in the carboxyl groups of long-chain fatty acids, suggesting that the latter had been synthesized from 2-carbon fragments formed from the oxidation of octanoate. In contrast, only a small fraction of the palmitate was elongated. The similarities and differences between the metabolism of octanoic and palmitic acid in liver and intestine, and the possible nutritional significance of octanoic acid are discussed.     

Metabolism of odd-numbered fatty acids and even-numbered fatty acids in mouse

Fatty acids are converted into energy via beta-oxidation. Although almost all natural occurring fatty acids are even-numbered, there are some odd-numbered fatty acids too. The details of the metabolism rate of odd-numbered fatty acids, however, are not clear. In the present study, we simultaneously administered a triacylglycerol containing four types of labeled even-numbered (palmitic acid and stearic acid) and odd-numbered (pentadecanoic acid and heptadecanoic acid) fatty acids to mice to compare the rates of their metabolism. The rates of metabolism were evaluated based on the accumulation of the labeled fatty acids in the small intestine epithelium, liver, and epididymal fat. Odd-numbered fatty acids accumulated mainly in the epididymal fat. In contrast, there was no accumulation of even-numbered fatty acids observed in the small intestine epithelium, liver, or epididymal fat. These results suggest that odd-numbered fatty acids might not be favorable substrates for beta-oxidation-related enzymes.     

Production and Emulsifying Effect of Polyglycerol and Fatty Acid Esters with Varying Degrees of Esterification

Esters with acyl groups can be formed by the esterification of polyglycerol. The purpose of the present study was to produce fatty acid esters [hexanoic (caproic), octanoic (caprylic), decanoic (capric), dodecanoic (lauric), tetradecanoic (myristic), hexadecanoic (palmitic), octadecanoic (stearic)] and polyglycerol (average number‐of degrees of polymerization of 5) with varying degrees of esterification and to examine their emulsifying properties. A number of fundamental catalysts of polyglycerol acylation reactions by methyl esters of carboxylic acid were studied, and sodium methoxide was found to be the best choice. The temperature rate of transesterification increased from 180 to 220 °C with the fatty acid chain alkyl residue. Synthesized mono‐, di‐, tri‐, tetra‐, and heptaesters of various fatty acids and polyglycerol provided the highest hydroxyl values from 15 to 815 mg KOH g^?1 and saponification values from 82 to 321 mg KOH g^?1. The emulsifying properties were assessed for all polyglycerol and fatty acid esters, with results showing maximum emulsifying effect for tri‐ and tetraesters of capric, lauric, and caprylic acids. Regardless of the hydrophilic–lipophilic balance value (HLB) of polyglycerol esters and carboxylic acid, a 4:1 ratio of sunflower oil to water formed a water‐in‐oil type emulsion. When mixing oil and water in a 1:1 ratio, mono‐ and diesters of polyglycerol formed an oil‐in‐water type emulsion, heptaesters formed a water‐in‐oil type emulsion, and tri‐ and tetraesters formed both of types of emulsions, depending on the length of the acid hydrocarbon radicals.     

Isovaleric acid as a precursor of odd numbered iso fatty acids in Tetrahymena

Tris isovalerate-supplementedTetrahymena pyriformis W showed no qualitative change in fatty acid composition; however, an increase in polar lipids that contain odd numbered iso acids (C₁₃, C₁₅, C₁₇, C₁₉) occurred. This change was accompanied by a decrease in the proportional amount of even numbered normal acids (C₁₄, C₁₆, C₁₈). The neutral and polar lipids from cells incubated with [1-¹⁴C] isovaleric acid were found to contain radioactivity. The methyl esters of the saturated fatty acids obtained from the polar lipids by alkaline methanolysis were separated by reversed phase chromatography, the identities confirmed by gas chromatography-mass spectrometry, and the specific activities determined. Iso acids were found to be the most heavily labeled materials. In addition to ceramide, two sphingolipid components were detected. One yielded saturated fatty acids after acidic methanolysis, while the other contained >93% α-hydroxy fatty acids. Radioactivity was noted in the long chain base fraction derived from the sphingolipids. Progressive growth inhibition occurred as the isovalerate concentration was increased in the culture medium; however, the ciliates were morphologically indistinguishable from unsupplemented cells.     

Total Synthesis and Structural Elucidation of Two Unusual Non-Methylene-Interrupted Fatty Acids in Ovaries of the Limpet <Emphasis Type="Italic">Cellana toreuma</Emphasis>

In our previous study, unusual odd‐numbered dienoic acids with a terminal olefin were found as minor components in ovaries of the Japanese limpet Cellana toreuma, and the synthetic interests have been focused onto their structural confirmation and the inspection into their potential biological activity. Here, we describe an efficient and stereoselective total synthesis of two new unusual dienoic acids, 19:2?7,18 and 21:2?7,20, through a common pathway involving the strategic combination of alkyne‐zipper reaction and Lindlar hydrogenation for the construction of their unique carbon chains. In our synthetic study, 2‐propyn‐1‐ol was at first subjected to alkylation and alkyne‐zipper reaction to form the two fragments, and the subsequent carbon chain elongation was achieved by the usual coupling reaction to obtain the C‐19 and C‐21 products bearing an internal acetylenic group. Then, the internal acetylenic group of these products was subjected to Lindlar hydrogenation to form a Z‐alkenyl moiety, and the subsequent deprotection of the products was carried out under an acidic condition without isomerization of the internal Z‐alkenyl group. Total synthesis of target fatty acids, 19:2?7,18 and 21:2?7,20, was finally accomplished by two‐step oxidation of the resulting alcohols into carboxylic acids in a highly chemoselective manner, and the structures of these unusual natural fatty acids were finally elucidated by identifying the GC–MS spectra of the methyl esters of authentic and synthetic fatty acids.     

Identification of Aromatic Fatty Acids in Butter Fat

Bovine milk fat contains a large variety of structurally different fatty acids. In this study, we describe the presence of aromatic fatty acids in a butter fat sample. Fatty acids were released from butter fat and converted into the corresponding methyl esters (FAME). Urea complexation was used to separate the main saturated fatty acids. GC/MS screening of the FAME in the filtrate of the urea complexation indicated the presence of aromatic fatty acids. By (1) conversion of two representatives into picolinyl esters which were analyzed by GC/MS, (2) linear log t_R over carbon number plots (R² = 0.95) and by the use of two reference standards we were able to show that the phenyl unit was located on the terminal carbon of the straight acyl chain of the FAME. In a fraction gathered by countercurrent chromatography we were able to identify 3‐phenylpropionic acid (Ph‐3:0), 4‐phenylbutyric acid (Ph‐4:0), 5‐phenylpentanoic acid (Ph‐5:0), 6‐phenylhexanoic acid (Ph‐6:0), 7‐phenylheptanoic acid (Ph‐7:0), 8‐phenyloctanoic acid (Ph‐8:0), 9‐phenylnonanoic acid (Ph‐9:0), 10‐phenyldecanoic acid (Ph‐10:0), 11‐phenylundecanoic acid (Ph‐11:0), 12‐phenyldodecanoic acid (Ph‐12:0), 13‐phenyltridecanoic acid (Ph‐13:0), along with one unsaturated phenyldecenoic acid (Ph‐10:1) isomer. Preliminary results indicate that the aromatic fatty acids may have been formed exogenously in the rumen of the cows. The total amount of the aromatic fatty acids was estimated at 0.15 mg/g butter fat, which corresponds with an average daily intake of ~5 mg per day in Germany and ~4.4 mg per day in Europe.     

Methyl Esters (Biodiesel) from and Fatty Acid Profile of Gliricidia sepium Seed Oil

Increasing the supply of biodiesel by defining and developing additional feedstocks is important to overcome the still limited amounts available of this alternative fuel. In this connection, the methyl esters of the seed oil of Gliricidia sepium were synthesized and the significant fuel‐related properties were determined. The fatty acid profile was also determined with saturated fatty acids comprising slightly more than 35 %, 16.5 % palmitic, 14.5 % stearic, as well as lesser amounts of even longer‐chain fatty acids. Linoleic acid is the most prominent acid at about 49 %. Corresponding to the high content of saturated fatty acid methyl esters, cold flow is the most problematic property as shown by a high cloud point of slightly >20 °C. Otherwise, the properties of G. sepium methyl esters are acceptable for biodiesel use when comparing them to specifications in biodiesel standards but the problematic cold flow properties would need to be observed. The ¹H‐ and ¹³C‐NMR spectra of G. sepium methyl esters are reported.     

Hepatic metabolism of 1-14C octanoic and 1-14C margaric acids

The hepatic metabolism of 1-¹⁴C margaric acid, a 17 carbon long chain saturated fatty acid which is present in the liver in trace amounts, was compared with 1-¹⁴C octanoic acid and 1-¹⁴C palmitic acid to determine if the enhanced oxidation of medium chain fatty acids to CO₂ was dependent on fatty acid chain length or the endogenous pool size of the fatty acid substrate. Despite the fact that endogenous margarate is present in trace amounts, there was no significant difference in the oxidation of margarate and palmitate to CO₂, while the oxidation of octanoate to CO₂ was significantly more rapid. Both margarate and palmitate were more readily incorporated into lipid soluble products in contrast to the low rate of incorporation of octanoate. However, margarate was less readily incorporated into triglyceride, phospholipid and monoglyceride than palmitate. These studies suggest that the chain length rather than hepatic content of the fatty acid determines whether the carboxyl group of equimolar amounts of a 1-¹⁴C-carboxyl labeled fatty acid will be preferentially oxidized to CO₂ or incorporated into tissue lipid in the liver.     

Fatty acid and conjugated linoleic acid isomer profiles in human milk fat

The fatty acid composition of 39 mature human milk samples from four Spanish women collected between 2 and 18 weeks during lactation was studied by gas chromatography. The conjugated linoleic acid (CLA) isomer profile was also determined by silver‐ion HPLC (Ag⁺‐HPLC) with three columns in series. The major fatty acid fraction in milk lipids throughout lactation was represented by the monounsaturated fatty acids, with oleic acid being the predominant compound (36–49% of total fatty acids). The saturated fatty acid fraction represented more than 35% of the total fatty acids, and polyunsaturated fatty acids ranged on average between 10 and 13%. Mean values of total CLA varied from 0.12 to 0.15% of total fatty acids. The complex mixture of CLA isomers was separated by Ag⁺‐HPLC. Rumenic acid (RA, cis‐9 trans‐11 C18:2) was the major isomer, representing more than 60% of total CLA. Trans‐9 trans‐11 and 7‐9 (cis‐trans + trans‐cis) C18:2 were the main CLA isomers after RA. Very small amounts of 8‐10 and 10‐12 C18:2 (cis‐trans + trans‐cis) isomers were detected, as were different proportions of cis‐11 trans‐13 and trans‐11 cis‐13 C18:2. Although most of the isomers were present in all samples, their concentrations varied considerably.     

Determination of fatty acids and some undesirable fatty acid isomers in selected Turkish margarines

The fatty acid composition and total trans fatty acid content in 10 margarines produced in Turkey were determined by capillary gas chromatography and Fourier transform‐infrared spectroscopy (FT‐IR) spectroscopy. The fatty acid composition ranged as follows: saturated fatty acids, C16:0 (palmitic) 11.3 to 31.8% and C18:0 (stearic) 5.7 to 8.7%, monounsaturated fatty acids, C18:1 (oleic) 21.8 to 35.7% and C18:1 trans isomers 0.4 to 27.4%, polyunsaturated fatty acid, C18:2 linoleic acid 5.2 to 40.2%. Some positional isomers of C18:1 as cis‐11‐octadecenoic acid varied from 0.7 to 4.6% and cis‐13 trace to 2.4%. The total trans fatty acid contents were between 0.9 and 32.0% when measured with capillary gas chromatography and between 0 and 30.2% with FT‐IR spectroscopy. Some of the margarines analyzed contained trace amount of trans fatty acids which could not be detected by FT‐IR spectroscopy.     

The biosynthesis of n-[2H7] fatty acids byArthrobacter globiformis from [U-2H15] octanoic acid

The principal fatty acids present whenArthrobacter globiformis is grown on a glycine medium free of normal fatty acids were found to be the C15 and C16 anteiso fatty acids; only a small amount of the normal fatty acids (C14 and C16) were present. Cells grown on the same medium but supplemented mented with 0.1 mg/ml [U-²H₁₅]octanoic acid were found to contain an increased amount of the normal fatty acids and these fatty acids were found to be labeled with 7 deuteriums. I concluded that the octanoic acid is degraded by β-oxidation in these cells to [U-²H₇] butyryl-CoA, which then competes with 2-methylbutyryl-CoA for the initiation of fatty acid biosynthesis.     

Serum lipid analysis and isotopic enrichment is suggestive of greater lipogenesis in young long-term cannabis users: A secondary analysis of a case–control study

Cannabis is now legal in many countries and while numerous studies have reported on its impact on cognition and appetite regulation, none have examined fatty acid metabolism in young cannabis users. We conducted an exploratory analysis to evaluate cannabis impact on fatty acid metabolism in cannabis users (n = 21) and non-cannabis users (n = 16). Serum levels of some saturated and monounsaturated fatty acids, including palmitic, palmitoleic, and oleic acids were higher in cannabis users compared to nonusers. As palmitic acid can be derived from diet or lipogenesis from sugars, we evaluated lipogenesis using a de novo lipogenesis index (palmitate/linoleic acid) and carbon-specific isotope analysis, which allows for the determination of fatty acid ¹³C signature. The significantly higher de novo lipogenesis index in the cannabis users group along with a more enriched ¹³C signature of palmitic acid suggested an increase in lipogenesis. In addition, while serum glucose concentration did not differ between groups, pyruvate and lactate were lower in the cannabis user group, with pyruvate negatively correlating with palmitic acid. Furthermore, the endocannabinoid 2-arachidonoylglycerol was elevated in cannabis users and could contribute to lipogenesis by activating the cannabinoid receptor 1. Because palmitic acid has been suggested to increase inflammation, we measured peripheral cytokines and observed no changes in inflammatory cytokines. Finally, an anti-inflammatory metabolite of palmitic acid, palmitoylethanolamide was elevated in cannabis users. Our results suggest that lipogenic activity is increased in cannabis users; however, future studies, including prospective studies that control dietary intake are required.     

Profiling and Imaging of Phospholipids in Brains of Abcd1‐Deficient Mice

ABCD1 is a gene responsible for X‐linked adrenoleukodystrophy (X‐ALD), and is critical for the transport of very long‐chain fatty acids (VLCFA) into peroxisomes and subsequent β‐oxidation. VLCFA‐containing lipids accumulate in X‐ALD patients, although the effect of ABCD1‐deficiency on each lipid species in the central nervous system has not been fully characterized. In this study, each phospholipid and lysophospholipid species in Abcd1‐deficient mice brains were profiled by liquid chromatography‐mass spectrometry. Among the phospholipid and lysophospholipid species that are significantly more enriched in Abcd1‐deficient mice brains, VLCFA were present in 75, 15, 5, 4, and 1 species of phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, lysophosphatidylcholine, and lysophosphatidylethanolamine, respectively. Most VLCFA were incorporated at the sn‐1 position of phosphatidylcholine and phosphatidylethanolamine. Among the phospholipid species that are significantly less enriched in Abcd1‐deficient mice brains, odd‐numbered saturated or mono‐unsaturated fatty acyl moieties are contained in all phosphatidylcholine species. In addition, a number of phosphatidylglycerol, phosphatidylinositol, and phosphatidylserine species contained highly unsaturated fatty acyl moieties. Intriguingly, 44:1 phosphatidylcholine with VLCFA was mainly distributed in the gray matter, such as the cortex, but not in the white matter in the cerebrum and cerebellum. These results show that ABCD1‐deficiency causes metabolic alternation of long‐chain fatty acids and VLCFA. Moreover, our results imply a molecular mechanism for the incorporation of saturated or monounsaturated VLCFA into the sn‐1 position of phospholipids, and also indicate that the distribution of phospholipids with VLCFA may correlate with the development of X‐ALD.     

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.     

A minor source of vernolic,malvalic, and sterculic acids inPithecollobium dulce (syn.Inga dulcis) seed oil

Pithecollobium dulce, Benth (syn.Inga dulcis, Willd) seed oil, belonging to the Leguminosae plant family, contains minor amounts of vernolic acid (12,13-epoxy-octadec-cis-9-enoic acid, 10.0%), malvalic acid [7-(2-octacyclopropen-1-yl)heptanoic acid, 3.2%], and sterculic acid [8-(2-octacyclopropen-1-yl)octanoic acid, 2.0%]. The other normal fatty acids are palmitic (12.1%), stearic (4.2%), behenic (10.6%), oleic (34.1%), and linoleic (23.8%). These fatty acids have been characterized by Fourier transform infrared,¹H nuclear magnetic resonance, mass spectrometry and gas-liquid chromatography techniques and by chemical degradations.     

Maternal High‐Fat‐Diet Programs Rat Offspring Liver Fatty Acid Metabolism

In offspring exposed in utero to a maternal diet high in fat (HF), we have previously demonstrated that despite similar birth weights, HF adult offspring at 6 months of age had significantly higher body weights, greater adiposity, and increased triacylglycerol (TAG) levels as compared to controls. We hypothesized that a maternal HF diet predisposes to offspring adiposity via a programmed increase in the synthesis of monounsaturated fatty acids in the liver and hence increased substrate availability for liver TAG synthesis. We further hypothesized that programmed changes in offspring liver fatty acid metabolism are associated with increased liver expression of the lipogenic enzyme stearoyl‐CoA desaturase‐1 (SCD‐1). Female rats were maintained on a HF diet rich in monounsaturated fatty acids (MUFA) prior to and throughout pregnancy and lactation. After birth, newborns were nursed by the same dam, and all offspring were weaned to control diet. Plasma and liver fatty acid compositions were determined using gas chromatography/mass spectrometry. Fatty acid C16 desaturation indices of palmitoleic/palmitic and (vaccenic + palmitoleic)/palmitic and the C18 desaturation index of oleic/stearic were calculated. Liver protein abundance of SCD‐1 was analyzed in newborns and adult offspring. Plasma and liver C16 desaturation indices were decreased in HF newborns, but increased in the adult offspring. Liver SCD‐1 expression was increased in the HF adult offspring. These data show that the maternal HF diet during pregnancy and lactation increases offspring liver SCD‐1 protein abundance and alters the liver C16 desaturase pathway.     

Identification of n‐6 Monounsaturated Fatty Acids in Acer Seed Oils

Seed oils from Acer species are a potential source of the nutraceutical fatty acids, nervonic acid (cis‐15‐tetracosenoic acid, NA), and γ‐linolenic acid (cis‐6,9,12‐octadecatrienoic acid, GLA). To further characterize the genus, seed fatty acid content and composition were determined for 20 species of Acer. Fatty acid content ranged from 8.2% for Acer macrophyllum to over 36% for A. mono and A. negundo. The presence of very‐long‐chain fatty acids (VLCFA), with chain length of 20‐carbons or greater, and GLA were characteristic features of the seed oils. In all species, erucic acid (cis‐13‐docosenoic acid, EA) was the predominant VLCFA with the highest level of NA being only 8.6% in A. olivianum. Regioselective lipase digestion demonstrated that VLCFA are largely absent from the sn‐2 position of seed triacylglycerol, whereas GLA is primarily located at this position. Five Acer species contained low levels (<2%) of cis‐12‐octadecenoic acid and cis‐14‐eicosenoic acid, uncommon n‐6 fatty acids not previously reported from Acer.     

Identification and Characterization of Phospholipids with Very Long Chain Fatty Acids in Brewer’s Yeast

Yeast lipids and fatty acids (FA) were analyzed in Saccharomyces pastorianus from seven breweries and in the dietary yeast supplement Pangamin. GC–MS identified more than 30 FA, half of which were very‐long chain fatty acids (VLCFA) with hydrocarbon chain lengths of ≥22 C atoms. Positional isomers ω‐9 and ω‐7 were identified in FA with C18–C28 even‐numbered alkyl chains. The most abundant ω‐7 isomer was cis‐vaccenic acid. The structure of monounsaturated FA was proved by dimethyl disulfide adducts (position of double bonds and cis geometric configuration) and by GC–MS of pyridyl carbinol esters. Ultra‐high performance liquid chromatography‐tandem mass spectrometry with negative electrospray ionization identified the phospholipids phosphatidylethanolamine, phosphatidylinositol and phosphatidylcholine, with more than 150 molecular species. Wild‐type unmutated brewer's yeast strains conventionally used for the manufacture of food supplements were found to contain VLCFA.     

Pristanic acid is activator of peroxisome proliferator activated receptor alpha

lsoprenoid phytanic acid (3,7,11,15‐tetramethylhexadecanoic acid) is degraded in peroxisomes by α‐oxidation to pristanic acid (2,6,10,14‐tetramethylpentadecanoic acid) and then via β‐oxidation. Branched‐chain phytanic acid is an activator of the peroxisome proliferator activated receptor α (PPAR ) which in liver cells regulates expression of genes encoding peroxisomal and mitochondrial β‐oxidative enzymes as well as cytosolic/nuclear liver‐type fatty acid binding protein (L‐FABP). In this report we address the question whether pristanic acid also acts as activator of PPARα and thus mediates the expression of its catabolizing enzymes. In a first in vivo approach we fed pristanic acid for 14 days to wildtype mice and to mice lacking sterol carrier protein 2/sterol carrier protein x which Ieads to a phenotype having high concentrations of branched‐chain fatty acids. In either genotype, feeding pristanic acid was associated with a strong induction of peroxisomal β‐oxidation enzymes tested (acyl‐CoA oxidase, bifunctional enzyme, thiolase) as well as of L‐FABP. The link between pristanic acid and protein expression observed was established by carrying out assays for transactivation of PPARα in transfected HepG2 cells. In comparison to hypolipidemic drugs and to straight‐chain fatty acids known to be PPARα agonists, branched‐chain phytanic and pristanic acids were substantially stronger activators, pristanic acid being even superior to phytanic acid.