High content of polyunsaturated fatty acids in muscle phospholipids of a fast runner,the European brown hare (Lepus europaeus)

To investigate both seasonal changes and possible intracorporal gradients of phospholipid fatty acid composition, skeletal muscles (n=124), hearts (n=27), and livers (n=34) from free-living brown hares (Lepus europaeus) were analyzed. Phospholipids from both skeletal muscles and heart had a high degree of unsaturation with 66.8±0.63% and 65.7±0.5% polyunsaturated fatty acids, respectively. This is the highest proportion of polyunsaturated fatty acids reported in any mammalian tissue. Polyunsaturated fatty acid content in skeletal muscles was 2.3% greater in winter compared to summer (F_1,106=17.7; P=0.0001), which may reflect thermoregulatory adjustments. Arachidonate (C20:4n-6) showed the greatest seasonal increase (+2.5%; F=7.95; P=0.0057). However, there were no pronounced differences in polyunsaturated fatty acid content between skeletal muscles from different locations in the body (m. iliopsoas, m. longissimus dorsi and m. vastus). Total muscle phospholipid polyunsaturated fatty acid content was correlated with polyunsaturated fatty acid content in triacyglycerols from perirenal white adipose tissue depots (r²=0.61; P=0.004). Polyunsaturated fatty acids were enriched in muscle phospholipids (56.8–73.6%), compared to white adipose tissue lipids (20.9–61.2%), and liver phospholipids (25.1–54.2%). We suggest that the high degree of muscle membrane unsaturation is related to hare-specific traits, such as a high maximum running speed.Abbreviations BMR basal metabolic rate - DPA docosapentaenoic acid - DHA docosahexaenoic acid - FA fatty acid - MUFA monounsaturated fatty acid - PC principal component - PUFA polyunsaturated fatty acid - SFA saturated fatty acid - UI unsaturation index - WAT white adipose tissueCommunicated by: G. Heldmaier     

Biosynthesis of polyunsaturated fatty acids in zooxanthellae and polyps of corals

The fatty acid (FA) composition of zooxanthellae, polyp tissue, and intact colonies was determined in soft coral Sinularia sp. and hard coral Acropora sp. Analysis of the distribution of polyunsaturated fatty acids (PUFAs) among the zooxanthellae and the host organism showed that 18: 3n-6 and C_18–22 PUFAs of the n-3 series (18: 4n-3, 20: 5n-3, 22: 5n-3, and 22: 6n-3) were mainly synthesized by the zooxanthellae and that C_20–22 PUFAs of the n-6 series (20: 3n-6, 20: 4n-6, and 22: 4n-6) were synthesized in the polyp tissue. Soft coral polyps were able to synthesize tetracosapolyenoic FAs (24: 5n-6 and 24: 6n-3) and 18: 2n-7, their zooxanthellae synthesized C₁₆ PUFAs (16: 2n-7, 16: 3n-4, and 16: 4n-1). It is supposed that the biosynthesis of 16: 2n-7 in Sinularia sp. and 18: 3n-6 in Acropora sp. is catalyzed by Δ6 desaturase. The relatively even distribution of three FAs (18: 2n-6, 18: 3n-6, and 16: 2n-7) among lipids of zooxanthellae and coral polyps indicates the possible transport of these FAs between symbionts and the host organism.     

Depression and adipose polyunsaturated fatty acids in an adolescent group

The purpose of the present study was to investigate the relation between adipose tissue polyunsaturated fatty acids, an index of long-term or habitual fatty acid dietary intake and depression. The sample consisted of 90 adolescents from the island of Crete. There were 54 girls and 36 boys, aged 13-18. The mean age was 15.2 years. Subjects were examined by the Preventive Medicine and Nutrition Clinic of the University of Crete. Depression was assessed through the use of the Beck Depression Inventory (BDI) and the Center for Epidemiologic Studies Depression Scale (CES-D). Unlike other studies, there were no significant relations between adipose tissue n-3 or n-6 polyunsaturated fatty acids and depression. BDI correlated positively with adipose tissue C20:3n-6/C18:3n-6 ratio, while CES-D correlated positively with adipose tissue (C20:3n-6+C22:5n-3)/(C18:3n-6+C20:5n-3) ratio. Depressed subjects (BDI>16, CES-D>16) had significantly elevated adipose tissue C20:3n-6/C18:3n-6 and (C20:3n-6+C22:5n-3)/(C18:3n-6+C20:5n-3) ratios, than non-depressed subjects. The observed positive relation between depression and the particular fatty acid ratios, in the present study, appears to indicate increasing activity of elongases, the enzymes responsible for elongating polyunsaturated fatty acids into their longer-chain derivatives, with increasing depression. This is the first literature report of a possible relation between elongases and depression. The observed relation may stem from a possible over-expression of the HELO1 (ELOVL5) gene, the gene encoding a protein responsible for elongating long-chain polyunsaturated fatty acids, in the adipose tissue of depressed adolescents.     

Enhancement of polyunsaturated fatty acid production by cerulenin treatment in polyunsaturated fatty acid-producing bacteria

When docosahexaenoic acid (DHA)-producing Moritella marina strain MP-1 was cultured in the medium containing 0.5 μ g cerulenin ml⁻¹, an inhibitor for fatty acid biosynthesis, the cells grew normally, but the␣content of DHA in the total fatty acids increased from 5.9–19.4%. The DHA yield of M. marina strain MP-1 cells also increased from 4 to 13.7 mg l⁻¹ by cerulenin treatment. The same effect of cerulenin was observed in eicosapentaenoic acid (EPA)-producing Shewanella marinintestina strain IK-1 grown in the medium containing 7.5 μg cerulenin ml⁻¹, and the cerulenin treatment increased the EPA yield from 1.6 to 8 mg l⁻¹. The use of cerulenin is, therefore, advantageous to increase the content of intracellular polyunsaturated fatty acids (PUFA) in particular PUFA-containing phospholipids in bacterial cells.An erratum to this article can be found at .     

Biosynthesis and bioavailability of long-chain polyunsaturated fatty acids in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) has a high occurrence in most countries. Recent studies estimate its prevalence to be near 30% in United States, Italian and Japanese general adult populations. NAFLD commonly presents along with obesity and insulin resistance (IR), pathologies that share with NAFLD metabolic and inflammatory components. These conditions, particularly NAFLD, are associated with alterations in the bioavailability of long-chain polyunsaturated fatty acids (LCPUFAs). In the human population, the bioavailability of LCPUFAs depends both on endogenous biosynthesis and diet amount of preformed LCPUFAs. However, the lower liver LCPUFAs product/precursor ratio namely (20:5n?3 + 22:6n?3)/18:3n?3, 20:4n?6/18:2n?6 present in common Western diets, makes critical an adequate pathway activity to ensure minimum bioavailability of LCPUFAs in most Western populations. The key step of this biosynthesis involves Δ5 and Δ6-desaturases, whose activities are altered in NAFLD. During the disease, the presence of molecular activators of these two enzymes does not correlate with the scarce LCPUFAS biosynthesis observed. The key to this apparent contradiction, or at least part of it, could be explained on the basis of the possible sensitivity of the desaturases to oxidative stress; a metabolic condition strongly linked to inflammatory pathologies such as NAFLD, obesity and IR and that, according to latest research, not only would be consequence but also possibly a cause of these diseases. The present review is focused on the relationship between NAFLD and the bioavailability of LCPUFAs, with special reference to the role that oxidative stress could play in the modulation of the liver fatty acid desaturase activity.     

Improved production of various polyunsaturated fatty acids through filamentous fungus Mortierella alpina breeding

Studies on the application of functional lipids such as polyunsaturated fatty acids (PUFAs) have proceeded in various fields regarding health and dietary requirements in a search for novel and rich sources. Filamentous fungus Mortierella alpina 1S-4 produces triacylglycerols rich in arachidonic acid, ones reaching 20 g/L and containing 30–70% arachidonic acid as to the total fatty acids. Mutants derived from M. alpina 1S-4, defective in Δ5 and Δ6 desaturases, accumulate triacylglycerols rich in unique PUFAs, i.e., dihomo-γ-linolenic acid and Mead acid, respectively. Furthermore, various mutants derived from M. alpina 1S-4 have led to the production of oils containing n−1, n−3, n−4, n−6, n−7, and n−9 PUFAs. A variety of genes encoding fatty acid desaturases and elongases involved in PUFA biosynthesis in M. alpina 1S-4 has been isolated and characterized. Molecular breeding of M. alpina strains by means of manipulation of these genes facilitates improvement of PUFA productivity and elucidation of the functions of enzymes involved in PUFA biosynthesis.     

Interannual and between species comparison of the lipids, fatty acids and sterols of Antarctic krill from the US AMLR Elephant Island survey area

Antarctic euphausiids, Euphausia superba, E. tricantha, E. frigida and Thysanoessa macrura were collected near Elephant Island ¦ during 1997 and 1998. Total lipid was highest in E. superba small juveniles (16 mg g⁻¹ wet mass), ranging from 12 to 15 mg in other euphausiids. Polar lipid (56–81% of total lipid) and triacylglycerol (12–38%) were the major lipids with wax esters (6%) only present in E. tricantha. Cholesterol was the major sterol (80–100% of total sterols) with desmosterol second in abundance (1–18%). 1997 T. macrura and E. superba contained a more diverse sterol profile, including 24-nordehydrocholesterol (0.1–1.7%), trans-dehydrocholesterol (1.1–1.5%), brassicasterol (0.5–1.7%), 24-methylenecholesterol (0.1–0.4%) and two stanols (0.1–0.2%). Monounsaturated fatty acids included primarily 18:1(n−9)c (7–21%), 18:1(n−7)c (3–13%) and 16:1(n−7)c (2–7%). The main saturated fatty acids in krill were 16:0 (18–29%), 14:0 (2–15%) and 18:0 (1–13%). Highest eicosapentaenoic acid [EPA, 20:5(n−3)] and docosahexaenoic acid [DHA, 22:6(n−3)] occurred in E. superba (EPA, 15–21%; DHA, 9–14%), and were less abundant in other krill. E. superba is a good source of EPA and DHA for consideration of direct or indirect use as a food item for human consumption. Lower levels of 18:4(n−3) in E. tricantha, E. frigida and T. macrura (0.4–0.7% of total fatty acids) are more consistent with a carnivorous or omnivorous diet as compared with herbivorous E. superba (3.7–9.4%). The polyunsaturated fatty acid (PUFA) 18:5(n−3) and the very-long chain (VLC-PUFA), C₂₆ and C₂₈ PUFA, were not present in 1997 samples, but were detected at low levels in most 1998 euphausiids. Interannual differences in these biomarkers suggest greater importance of dinoflagellates or some other phytoplankton group in the Elephant Island area during 1998. The data have enabled between year comparisons of trophodynamic interactions of krill collected in the Elephant Island region, and will be of use to groups using signature lipid methodology.     

Alpha-linolenic acid and its conversion to longer chain n−3 fatty acids: Benefits for human health and a role in maintaining tissue n−3 fatty acid levels

There is little doubt regarding the essential nature of alpha-linolenic acid (ALA), yet the capacity of dietary ALA to maintain adequate tissue levels of long chain n−3 fatty acids remains quite controversial. This simple point remains highly debated despite evidence that removal of dietary ALA promotes n−3 fatty acid inadequacy, including that of docosahexaenoic acid (DHA), and that many experiments demonstrate that dietary inclusion of ALA raises n−3 tissue fatty acid content, including DHA. Herein we propose, based upon our previous work and that of others, that ALA is elongated and desaturated in a tissue-dependent manner. One important concept is to recognize that ALA, like many other fatty acids, rapidly undergoes β-oxidation and that the carbons are conserved and reused for synthesis of other products including cholesterol and fatty acids. This process and the differences between utilization of dietary DHA or liver-derived DHA as compared to ALA have led to the dogma that ALA is not a useful fatty acid for maintaining tissue long chain n−3 fatty acids, including DHA. Herein, we propose that indeed dietary ALA is a crucial dietary source of n−3 fatty acids and its dietary inclusion is critical for maintaining tissue long chain n−3 levels.     

Polyunsaturated fatty acids of mosquitos reared with single dietary polyunsaturates

Stock adults of Culex pipiens and tarsalis reared in crude media had a third of their phospholipid fatty acids as polyunsaturates, mainly 18C but including prominent proportions of arachidonic (20:4n6) and eicosapentaenoic (20:5n3) acids. Adults reared with synthetic media devoid of polyunsaturated fatty acids and therefore unable to fly at emergence contained no more than trace amounts of any polyunsaturate. With synthetic media containing single polyunsaturates the following findings emerged. Of four polyunsaturates known to be highly effective essential fatty acids individually 20:4n6 or 20:5n3 appeared unchanged in tissue phospholipids in proportions reflecting dietary concentrations; dietary 22:4n6 or 22:6n3 (docosahexaenoic acid) appeared also as 20:4n6 or 20:5n3, respectively, retroconverted from the administered dietary fatty acids, which were detected only in traces. Two moderately effective dietary fatty acids, 18:3n6 (γ-linolenic) and 20:3n6 (homo-γ-linolenic), which support weak flight at emergence, appeared in tissue phospholipids respectively as 18:3n6 only, or as similar proportions of 18:3n6 and 20:3n6, this latter indicating shortening to the 18C analogue as well as accumulation of the dietary 20C acid. Six other polyunsaturates [18:2n6 (linoleic), 18:3n3 (linolenic) and their 20C and 22C analogues], all considered slightly effective as essential fatty acids although unable to support proper flight, appeared in tissue phospholipid in dose-related proportions as the 18C basal n6 or n3 family analogues, with only traces of the higher analogues when these were the dietary fatty acids provided, indicating sequential chain shortening within each series, n6 or n3, no interconversion of n6 and n3 members (also shown by all other data), and efficient accumulation of the resultant 18C polyunsaturates. These findings show no capability for de novo synthesis of polyunsaturated fatty acids, afford an insight into the metabolic interrelations of diet-derived polyunsaturates and indicate a primary importance for endogenous arachidonic and eicosapentaenoic acids in mosquito essential fatty acid physiology.     

Age-related changes of n-3 and n-6 polyunsaturated fatty acids in the anterior cingulate cortex of individuals with major depressive disorder

Accumulating evidence finds a relative deficiency of peripheral membrane fatty acids in persons with affective disorders such as unipolar and bipolar depression. Here we sought to investigate whether postmortem brain fatty acids within the anterior cingulate cortex (BA-24) varied according to the presence of major depression at the time of death. Using capillary gas chromatography we measured fatty acids in a depressed group (n=12), and in a control group without lifetime history of psychiatric diagnosis (n=14). Compared to the control group, the depressed group showed significantly lower concentrations of numerous saturated and polyunsaturated fatty acids including both the n-3 and n-6 fatty acids. Additionally, significant correlations between age at death and precursor (or metabolites) in the n-3 fatty acid pathway were demonstrated in the depressed group but not in control subjects. In the n-6 fatty acid family, the ratio of 20:3(n-6)/18:2(n-6) was higher in patients than in control groups, whereas the ratio of 20:4(n-6)/20:3(n-6) was relatively decreased in patients. Lastly, a significant negative correlation between age and the ratio of 20:4(n-6) to 22:6(n-3) was found in patients, but not in controls. Taken together, decreases in 22:6(n-3) may be caused, at least in part, by the diminished formation of 20:5(n-3), which is derived from 20:4(n-3) through a Δ5 desaturase reaction. The present findings from postmortem brain tissue raise the possibility that an increased ratio of 20:4(n-6) to 22:6(n-3) may provide us with a biomarker for depression. Future research should further investigate these relationships.     

Differences in growth,total lipid content and fatty acid composition among 60 clones of <Emphasis Type="Italic">Cylindrotheca fusiformis</Emphasis>

Differences between clones of the diatom Cylindrotheca fusiformi were studied with respect to growth rate, total lipid content and fatty acid composition. Sixty clones were isolated and cultivated under batch conditions. All clones were grown under identical conditions (temperature 22±1°C, light intensity 100 μmol photon m⁻² s⁻¹, salinity 28, F/2 medium) and were harvested in the late exponential growth phase for lipid and fatty acid analysis. The results show a wide variation in growth, total lipid content and fatty acid profiles among clones (p<0.05). The major fatty acids in the 60 clones were 14:0 (4.6–9.1%), 16:0 (18.2–32.0%), 16:1n-7 (21.6–33.1%), 20:4n-6 (4.1–13.5%) and 20:5n-3 (6.2–17.2%), with the highest proportion of 20:4n-6 in clone CF13 (13.5%), and the highest proportion of 20:5n-3 in clone CF5 (17.2%). The results support the view that some microalgal fatty acid variation is not restricted to interspecific variation and external factors, but also varies from clone to clone within the same species.     

Improvement of polyunsaturated fatty acids synthesis by the coexpression of CYB5 with desaturase genes in Saccharomyces cerevisiae

Since Saccharomyces cerevisiae contains Δ9 fatty acid desaturase (OLE1) as a sole fatty acid desaturase, it produces saturated and monounsaturated fatty acids of 16- and 18-carbon compounds. We showed earlier that Kluyveromyces lactis Δ12 (KlFAD2) and ω3 (KlFAD3) fatty acid desaturase genes enabled S. cerevisiae to make also polyunsaturated fatty acids (PUFAs), linoleic (18:2n-6), and α-linolenic (18:3n-3) acids. Unlike Δ9 fatty acid desaturase Ole1p, the two added fatty acid desaturases (KlFAD2and KlFAD3) do not contain a cytochrome b5 domain, and we now report on effects of the overexpression of K. lactis and S. cerevisiae cytochrome b5 (CYB5) genes as well as temperature effects on PUFA synthesis. Without extra cytochrome b5, while PUFA synthesis is significant at low temperature (20 °C), it was marginal at 30 °C. Overexpression of cytochrome b5 at 20 °C did not affect the fatty acid synthesis so much, but it significantly enhanced the synthesis of PUFA at 30 °C.     

Effect of maternal fat reserves on the fatty acid composition of sardine (Sardina pilchardus) oocytes

We compared the fatty acid (FA) composition of the muscle and gonads of female Iberian sardines with hydrated oocytes collected during the 2002/03 spawning season off southern Portugal (November and February) and off western Portugal (February). Sardine condition and total FA concentration in the muscle decreased between the two sampling dates, while the gonadosomatic index was similar between samples. Total monounsaturated FA concentrations in sardine gonads were different for the three samples while saturated and polyunsaturated FA concentrations were similar. Significant linear relations were found between FA concentrations in female muscle and oocytes, including eicosapentaenoic acid (EPA; 20:5n − 3) and arachidonic acid (AA; 20:4n − 6), both being essential for normal larval development. The concentration of docosahexaenoic acid (DHA; 22:6n − 3) in oocytes was independent on muscle concentration, probably resulting from its selective transfer to the oocytes. The EPA/DHA ratio was highly conserved in sardine tissues, while DHA/AA and EPA/AA ratios varied significantly between samples. These results indicate that the FA content of eggs produced by sardines varies throughout the spawning season, egg FA concentrations decreasing as females lose condition, and FA composition also shows spatial variability. Both types of variability may have a significant impact on egg quality, particularly on the amount of reserves available to larvae affecting their resistance to starvation, and the appropriate FA composition required for normal growth.     

Phospholipid fatty acid composition of gorgonians of the genus Pseudopterogorgia: Identification of tetracosapolyenoic acids

The phospholipid fatty acid composition of the Caribbean gorgonians Pseudopterogorgia acerosa (Pallas), Pseudopterogorgia americana (Gmelin), Pseudopterogorgia bipinnata (Verrill) and Pseudopterogorgia rigida (Bielschowsky) is described for the first time. The main phospholipids identified were phosphatidylethanolamine, phosphatidylcholine and phosphatidylserine. All four gorgonians presented a similar phospholipid fatty acid composition. The main fatty acids were 16:0, 18:3(n-6), 18:4(n-3), 20:4(n-6), 22:6(n-3), 24:5(n-6) and 24:6(n-3). In all of the studied Pseudopterogorgia gorgonians, high amounts of the tetracosapolyenoic fatty acids 24:5(n-6) and 24:6(n-3) were identified. In the four gorgonians studied, n-6 polyunsaturated fatty acids predominated. These results suggest that the occurrence of tetracosapolyenoic fatty acids in the Gorgoniidae is more general than previously recognized.     

Elongation of polyunsaturated fatty acids in trypanosomatids

Leishmania major synthesizes polyunsaturated fatty acids by using Delta6, Delta5 and Delta4 front-end desaturases, which have recently been characterized [Tripodi KE, Buttigliero LV, Altabe SG & Uttaro AD (2006) FEBS J273, 271-280], and two predicted elongases specific for C18 Delta6 and C20 Delta5 polyunsaturated fatty acids, respectively. Trypanosoma brucei and Trypanosoma cruzi lack Delta6 and Delta5 desaturases but contain Delta4 desaturases, implying that trypanosomes use exogenous polyunsaturated fatty acids to produce C22 Delta4 fatty acids. In order to identify putative precursors of these C22 fatty acids and to completely describe the pathways for polyunsaturated fatty acid biosynthesis in trypanosomatids, we have performed a search in the three genomes and identified four different elongase genes in T. brucei, five in T. cruzi and 14 in L. major. After a phylogenetic analysis of the encoded proteins together with elongases from a variety of other organisms, we selected four candidate polyunsaturated fatty acid elongases. Leishmania major CAJ02037, T. brucei AAX69821 and T. cruzi XP_808770 share 57-52% identity, and group together with C20 Delta5 polyunsaturated fatty acid elongases from algae. The predicted activity was corroborated by functional characterization after expression in yeast. T. brucei elongase was also able to elongate Delta8 and Delta11 C20 polyunsaturated fatty acids. L. major CAJ08636, which shares 33% identity with Mortierella alpinaDelta6 elongase, showed a high specificity for C18 Delta6 polyunsaturated fatty acids. In all cases, a preference for n6 polyunsaturated fatty acids was observed. This indicates that L. major has, as predicted, Delta6 and Delta5 elongases and a complete pathway for polyunsaturated fatty acid biosynthesis. Trypanosomes contain only Delta5 elongases, which, together with Delta4 desaturases, allow them to use eicosapentaenoic acid and arachidonic acid, a precursor that is relatively abundant in the host, for C22 polyunsaturated fatty acid biosynthesis.     

Metabolism of long-chain polyunsaturated fatty acids in isolated cardiac myocytes

The uptake and integrated intracellular metabolism of (n - 6) and (n - 3) polyunsaturated fatty acids was studied in isolated rat cardiac myocytes and in the perfused heart. Labeled linolenic acid (18:3(n - 3)) uptake and its subsequent metabolism into carbon dioxide as well as acylation into lipids was nonsaturable over a substrate range of 0.02 to 0.4 mM. [1-14C]Linoleic acid (18:2(n - 6)), dihomo-gamma-linolenic acid (20:3(n - 6)) and arachidonic acid (20:4(n - 6)) were transported into myocytes at rates similar to those for linolenic acid. Conversely both [1-14C]-gamma-linolenic acid (18:3(n - 6)) and eicosapentaenoic acid (20:5(n - 3)) were taken up at a slower rate. Oxidation of 18:3(n - 6) was 4-5-fold greater when compared with C18-C20 polyunsaturated fatty acids. When myocytes were incubated with labeled 18:2(n - 6), 18:3(n - 6), 18:3(n - 3), 20:4(n - 6) or 20:5(n - 3), it was not possible to detect any desaturation or chain-elongation products. Identical results were obtained when hearts were perfused with 1-14C-labeled linoleic acid.     

Successful high‐level accumulation of fish oil omega‐3 long‐chain polyunsaturated fatty acids in a transgenic oilseed crop

Omega‐3 (also called n‐3) long‐chain polyunsaturated fatty acids (≥C20; LC‐PUFAs) are of considerable interest, based on clear evidence of dietary health benefits and the concurrent decline of global sources (fish oils). Generating alternative transgenic plant sources of omega‐3 LC‐PUFAs, i.e. eicosapentaenoic acid (20:5 n‐3, EPA) and docosahexaenoic acid (22:6 n‐3, DHA) has previously proved problematic. Here we describe a set of heterologous genes capable of efficiently directing synthesis of these fatty acids in the seed oil of the crop Camelina sativa, while simultaneously avoiding accumulation of undesirable intermediate fatty acids. We describe two iterations: RRes_EPA in which seeds contain EPA levels of up to 31% (mean 24%), and RRes_DHA, in which seeds accumulate up to 12% EPA and 14% DHA (mean 11% EPA and 8% DHA). These omega‐3 LC‐PUFA levels are equivalent to those in fish oils, and represent a sustainable, terrestrial source of these fatty acids. We also describe the distribution of these non‐native fatty acids within C. sativa seed lipids, and consider these data in the context of our current understanding of acyl exchange during seed oil synthesis.     

Plasma polyunsaturated fatty acids and regional cerebral glucose metabolism in major depression

Deficiencies in polyunsaturated essential fatty acids (PUFA) are implicated in mood disorders, although mechanisms of action and regional specificity in the brain are unknown. We hypothesized that plasma phospholipid PUFA levels are correlated with regionally specific relative cerebral metabolic rates of glucose (rCMRglu). Medication-free depressed subjects (N=29) were studied using [¹⁸F]-fluoro-2-deoxyglucose positron emission tomography. Docosahexaenoic acid (22:6n-3), arachidonic acid (20:4n-6), and eicosapentaenoic acid (20:5n-3) were assessed as a percentage of total phospholipid PUFA (DHA%, AA%, and EPA%, respectively). DHA% and AA% correlated positively with rCMRglu in temporoparietal cortex. In addition, DHA% correlated negatively with rCMRglu in prefrontal cortex and anterior cingulate. No correlations were seen with EPA%. Thus, under conditions of low plasma DHA, rCMRglu was higher in temporoparietal cortex and lower in anterior cingulate/prefrontal cortex. Opposing effects of DHA on these regions is a hypothesis that could be addressed in future prospective studies with n-3 supplementation. This pilot study is the first to demonstrate fatty acid and regionally specific correlations in the brain between plasma PUFA and rCMRglu in humans.     

Incorporation of ω6 polyunsaturated fatty acids into phospholipids of the crab Carcinus maenas

The incorporation in vivo of ¹⁴C-18:2 ω6 and ³H-20:4 ω6 fatty acids in phospholipids isolated from gills, hepatopancreas and hemolymph of the crab Carcinus maenas was analysed. PC was the most heavily labelled phospholipid from these ω6-unsaturated fatty acids and appeared to play an important part in the phospholipids metabolism in Crustaceans. The pathway of fatty acids synthesis in phospholipids of C. maenas seems to be similar to those described for mammals. It is at the level of tissue Pl of C. maenas that the renewal of the 20:4 ω6 fatty acid is the most important. It is suggested that the rapid reorganization of phospholipid molecular species composition in the crab is checked by deacylation—reacylation cycle.     

The function of very long chain polyunsaturated fatty acids in the pineal gland

The mammalian pineal gland is a prominent secretory organ with a high metabolic activity. Melatonin (N-acetyl-5-methoxytryptamine), the main secretory product of the pineal gland, efficiently scavenges both the hydroxyl and peroxyl radicals counteracting lipid peroxidation in biological membranes. Approximately 25% of the total fatty acids present in the rat pineal lipids are represented by arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3). These very long chain polyunsaturated fatty acids play important roles in the pineal gland. In addition to the production of melatonin, the mammalian pineal gland is able of convert these polyunsaturated fatty acids into bioactive lipid mediators. Lipoxygenation is the principal lipoxygenase (LOX) activity observed in the rat pineal gland. Lipoxygenation in the pineal gland is exceptional because no other brain regions express significant LOX activities under normal physiological conditions. The rat pineal gland expresses both 12- and 15-lipoxygenase (LOX) activities, producing 12- and 15-hydroperoxyeicosatetraenoic acid (12- and 15-HpETE) from arachidonic acid and 14- and 17-hydroxydocosahexaenoic acid (14- and 17-HdoHE) from docosahexaenoic acid, respectively. The rat pineal also produces hepoxilins via LOX pathways. The hepoxilins are bioactive epoxy-hydroxy products of the arachidonic acid metabolism via the 12S-lipoxygenase (12S-LOX) pathway. The two key pineal biochemical functions, lipoxygenation and melatonin synthesis, may be synergistically regulated by the status of n-3 essential fatty acids.