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1.  Distribution of Polyunsaturated Fatty Acids in Bacteria Present in Intestines of Deep-Sea Fish and Shallow-Sea Poikilothermic Animals 
The lipid and fatty acid compositions in nine obligate and facultative barophilic bacteria isolated from the intestinal contents of seven deep-sea fish were determined. Phospholipid compositions were simple, with phosphatidylethanolamine and phosphatidylglycerol predominating in all strains. Docosahexaenoic acid (DHA; 22:6n-3), which has not been reported in procaryotes except for deep-sea bacteria, was found to be present in eight strains at a level of 8.1 to 21.5% of total fatty acids. In the other strain, eicosapentaenoic acid (EPA; 20:5n-3) was present at a level of 31.5% of total fatty acids. Other fatty acids observed in all strains were typical of marine gram-negative bacteria. Subcultures from pouches prepared from intestinal contents of five deep-sea fish by the most-probable-number (MPN) method were analyzed for fatty acids, and all subcultures contained DHA and/or EPA. Accordingly, viable cell counts of bacteria containing DHA and EPA were estimated at a maximum of 1.3 x 10(sup8) and 2.4 x 10(sup8) cells per ml, respectively, and accounted for 14 and 30%, respectively, of the total cell counts in the intestinal contents of the deep-sea fish. In the case of 10 shallow-sea poikilothermic animals having bacterial populations of 1.1 x 10(sup6) to 1.9 x 10(sup9) CFU per ml in intestinal contents, no DHA was found in the 112 isolates examined, while production of EPA was found in 40 isolates from cold- and temperate-sea samples. These results suggest that DHA and EPA are involved in some adaptations of bacteria to low temperature and high pressure.
PMCID: PMC1389193  PMID: 16535638
2.  Biochemical Function and Ecological Significance of Novel Bacterial Lipids in Deep-Sea Procaryotes 
The fatty acid composition of the membrane lipids in 11 deep-sea bacterial isolates was determined. The fatty acids observed were typical of marine vibrios except for the presence of large amounts of long-chain polyunsaturated fatty acids (PUFAs). These long-chain PUFAs were previously thought to be absent in procaryotes, with the notable exception of a single marine Flexibacter sp. In three barophilic strains tested at 2°C, there was a general increase in the relative amount of PUFAs as pressure was increased from a low growth pressure towards the optimal growth pressure. In Vibrio marinus MP-1, a psychrophilic strain, PUFAs were found to increase as a function of decreasing temperature at constant atmospheric pressure. These results suggest the involvement of PUFAs in the maintenance of optimal membrane fluidity and function over environmentally relevant temperatures and pressures. Furthermore, since these lipids are essential nutrients for higher taxa and are found in large amounts in the lipids of deep-sea vertebrates and invertebrates, an important, specific role for deep-sea bacteria in abyssal food webs is implicated.
PMCID: PMC238956  PMID: 16347037
3.  Starvation Response of the Marine Barophile CNPT-3 
The psychrophilic marine barophile CNPT-3 underwent a starvation-survival response similar to that reported for the marine bacteria Ant-300, DW1, and S-14. The number of culturable cells increased initially and then decreased gradually over a 24-day starvation period, with corresponding decreases in total cell number and direct viability count. A significant reduction in cell size and biovolume accompanied these changes. Starved cells demonstrated a greater tendency to attach at the in situ pressure (400 atm; ca. 40.5 MPa) and temperature (5°C) than at 1 atm (ca. 101 kPa), and the extent of attachment increased with increasing duration of starvation. The membrane fatty acid profile of the marine barophile CNPT-3 was studied as the cells were subjected to starvation conditions. A 37.5% increase in saturated fatty acids was observed during the first 8 days of starvation, with a concomitant decrease in unsaturated fatty acids. There was also an increase in the amount of short-chain (
PMCID: PMC195799  PMID: 16348747
A trans unsaturated fatty acid was found as a major constituent in the lipids of Pseudomonas putida P8. The fatty acid was identified as 9-trans-hexadecenoic acid by gas chromatography, argentation thin-layer chromatography, and infrared absorption spectrometry. Growing cells of P. putida P8 reacted to the presence of sublethal concentrations of phenol in the medium with changes in the fatty acid composition of the lipids, thereby increasing the degree of saturation. At phenol concentrations which completely inhibited the growth of P. putida, the cells were still able to increase the content of the trans unsaturated fatty acid and simultaneously to decrease the proportion of the corresponding 9-cis-hexadecenoic acid. This conversion of fatty acids was also induced by 4-chlorophenol in nongrowing cells in which the de novo synthesis of lipids had stopped, as shown by incorporation experiments with labeled acetate. The isomerization of the double bond in the presence of chloramphenicol indicates a constitutively operating enzyme system. The cis-to-trans modification of the fatty acids studied here apparently is a new way of adapting the membrane fluidity to the presence of phenols, thereby compensating for the elevation of membrane permeability induced by these toxic substances.
PMCID: PMC195693  PMID: 1622260
Journal of Bacteriology  1982;151(2):996-1005.
The lipids and fatty acids of Bordetella pertussis (phases I to IV) were analyzed by thin-layer chromatography, gas-liquid chromatography, and mass spectrometry and compared with those of B. parapertussis and B. bronchiseptica. The major lipid components of the three species were phosphatidylethanolamine, cardiolipin, phosphatidylglycerol, lysophosphatidylethanolamine, and an ornithine-containing lipid. The ornithine-containing lipid was characteristic of the genus Bordetella. The fatty acid composition of the total extractable cellular lipids of B. pertussis was mostly hexadecanoic and hexadecenoic acids (90%) in a ratio of about 1:1. The hexadecenoic acid of B. pertussis was in the cis-9 form. The fatty acid composition of the residual bound lipids was distinctly different from that of the extractable lipids, and residual bound lipids being mainly 3-hydroxytetradecanoic, tetradecanoic, and 3-hydroxydecanoic acids, with 3-hydroxydodecanoic acid occurring in some strains. It was determined that the 3-hydroxy fatty acids were derived from lipid A. The fatty acid composition of the total extractable cellular lipids of B. parapertussis and B. bronchiseptica, mainly composed of hexadecanoic and heptadecacyclopropanoic acid, differed from that of B. pertussis. Although the fatty acid composition of the residual bound lipids of B. parapertussis was similar to that of the residual bound lipids of B. pertussis, 2-hydroxydodecanoic acid was detected only in the bound lipids of B. bronchiseptica.
PMCID: PMC220353  PMID: 6284719
Journal of Bacteriology  1974;120(1):131-138.
The complex lipids and fatty acids of the seven type species of green bacteria and three strains of Chloroflexus aurantiacus were analyzed. The green bacteria contained lipids that behaved as cardiolipin and phosphatidylglycerol on thin-layer chromatography. They did not contain phosphatidylethanolamine or phosphatidylserine. Similarly, Chloroflexus contained lipids that behaved as phosphatidylglycerol and phosphatidylinositol on thin-layer chromatography and did not contain phosphatidylethanolamine or phosphatidylserine. The green bacteria contained glycolipids I and II of Constantopoulos and Bloch (monogalactosyldiglyceride and a galactose- and rhamnose-containing diglyceride). Chloroflexus exhibited galactose-containing glycolipids that behaved identically with the mono- and digalactosyldiglycerides of spinach on thin-layer chromatography, and each contained galactose as well as at least one other sugar. The fatty acids of both groups of bacteria consisted entirely of saturated and monounsaturated fatty acids. In the green bacteria, myristic, palmitic, and hexadecenoic acids predominated. In Chloroflexus, palmitic, stearic, and oleic acids predominated. The positions of the double bonds in the monounsaturated fatty acids of Chloroflexus indicated synthesis by the anaerobic pathway. The lipid analyses suggest a close relationship between the green bacteria and Chloroflexus and further suggest that these groups of photosynthetic bacteria are more closely related to the blue-green algae than are the purple bacteria.
PMCID: PMC245741  PMID: 4421249
Journal of Bacteriology  1983;153(3):1348-1351.
We investigated the lipid composition of vegetative cells of Stigmatella aurantiaca. Four phospholipids were isolated and identified: phosphatidylethanolamine as the main component, phosphatidylglycerol, lysophosphatidylethanolamine in an exceptionally large amount (17%), and phosphatidylinositol (18 to 25%), rare in procaryotic cells. This composition did not change significantly during growth. The fatty acids of total lipids were found to be rather similar to those of other strains of myxobacteria; the main fatty acids found were unsaturated and branched. We noted a different fatty acid pattern for each phospholipid. The presence of unusual alkyl ether linkages, established by chemical hydrolysis and infrared spectroscopy, was unexpected in these bacteria. Diacyl ester, dialkyl ether, and monoacyl-monoalkyl structures were shown in phosphatidylethanolamine and phosphatidylglycerol. Lysophosphatidylethanolamine was essentially a monoacyl form, whereas phosphatidylinositol was a unique dialkyl ether phospholipid.
PMCID: PMC221784  PMID: 6402494
Consumption of ω-3 fatty acids from fish oil, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), decreases risk for heart failure and attenuates pathologic cardiac remodeling in response to pressure overload. Dietary supplementation with EPA+DHA may also impact cardiac mitochondrial function and energetics through alteration of membrane phospholipids. We assessed the role of EPA+DHA supplementation on left ventricular (LV) function, cardiac mitochondrial membrane phospholipid composition, respiration, and sensitivity to mitochondrial permeability transition pore (MPTP) opening in normal and infarcted myocardium. Rats were subjected to sham surgery or myocardial infarction by coronary artery ligation (n=10–14), and fed a standard diet, or supplemented with EPA+DHA (2.3% of energy intake) for 12 weeks. EPA+DHA altered fatty acid composition of total mitochondrial phospholipids and cardiolipin by reducing arachidonic acid content and increasing DHA incorporation. EPA+DHA significantly increased calcium uptake capacity in both subsarcolemmal and intrafibrillar mitochondria from sham rats. This treatment effect persisted with the addition of cyclosporin A, and was not accompanied by changes in mitochondrial respiration or coupling, or cyclophilin D protein expression. Myocardial infarction resulted in heart failure as evidenced by LV dilation and contractile dysfunction. Infarcted LV myocardium had decreased mitochondrial protein yield and activity of mitochondrial marker enzymes, however respiratory function of isolated mitochondria was normal. EPA+DHA had no effect on LV function, mitochondrial respiration, or MPTP opening in rats with heart failure. In conclusion, dietary supplementation with EPA+DHA altered mitochondrial membrane phospholipid fatty acid composition in normal and infarcted hearts, but delayed MPTP opening only in normal hearts.
PMCID: PMC2783943  PMID: 19703463
eicosapentaenoic acid; docosahexaenoic acid; myocardial infarction; mitochondrial permeability transition pore
Faraday discussions  2013;161:461-589.
Poly-unsaturated fatty acids (PUFAs) alter the function of many membrane proteins, whereas monounsatured fatty acids generally are inert. We previously showed that docosahexaenoic acid (DHA) at pH 7 decreases the bilayer stiffness, consistent with an amphiphile-induced increase in elasticity, but not with a negative change in curvature; oleic acid (OA) was inert (Bruno, Koeppe and Andersen, Proc. Natl. Acad. Sci. USA 104:9638–9643, 2007). To further explore how PUFAs and other amphiphiles may alter lipid bilayer properties, and thus membrane protein function, we examined how changes in acyl chain unsaturation, and head group charge and size, alter bilayer properties, as sensed by bilayer-spanning gramicidin A (gA) channels of different lengths. Compared to DHA, the neutral DHA-methyl ester has reduced effects on bilayer properties, and 1-palmitoyl-2-docosahexaenoyl-phosphatidylcholine (PDPC) forms bilayers that are softer than dioleoylphosphatidylcholine (DOPC). The changes in channel function are larger for the short gA channels, indicating that changes in elasticity dominate over changes in curvature. We altered the fatty acid protonation by titration: docosahexaenoic acid (DHA) is more potent at pH 9 (relative to pH 7) and is inert at pH 4; OA, which was inert at pH 7, becomes a potent modifier of bilayer properties at pH 9. At both pH 7 and 9, DHA and OA produced larger changes in the lifetimes of the short gA channels, demonstrating that they increase lipid bilayer elasticity when deprotonated—though OA promotes the formation of inverted hexagonal phases at pH 7. The positively charged oleylamine (OAm), which has a small head-group and therefore should be a negative curvature promoter, inhibited gA channel function, with similar reductions in the lifetimes of the short and long gA channels, indicating a curvature-dominated effect. Monitoring the single-channel conductance, we find that the negatively charged fatty acids increase the conductance by increasing the local negative charge around the channel, whereas the positively charged OAm has no effect. These results suggest that deprotonated fatty acids increase bilayer elasticity by reversibly adsorbing at the bilayer/solution interface.
PMCID: PMC3703894  PMID: 23805753
PLoS ONE  2012;7(12):e51994.
Obesity increases risk for cardiomyopathy in the absence of hypertension, diabetes or ischemia. The fatty acid milieu, modulated by diet, may modify myocardial structure and function, lending partial explanation for the array of cardiomyopathic phenotypy. We sought to identify gross, cellular and ultrastructural myocardial changes associated with Western diet intake, and subsequent modification with docosahexaenoic acid (DHA) supplementation. Wistar and Sprague-Dawley (SD) rats received 1 of 3 diets: control (CON); Western (WES); Western + DHA (WES+DHA). After 12 weeks of treatment, echocardiography was performed and myocardial adiponectin, fatty acids, collagen, area occupied by lipid and myocytes, and ultrastructure were determined. Strain effects included higher serum adiponectin in Wistar rats, and differences in myocardial fatty acid composition. Diet effects were evident in that both WES and WES+DHA feeding were associated with similarly increased left ventricular (LV) diastolic cranial wall thickness (LVWcr/d) and decreased diastolic internal diameter (LVIDd), compared to CON. Unexpectedly, WES+DHA feeding was associated additionally with increased thickness of the LV cranial wall during systole (LVWcr/s) and the caudal wall during diastole (LVWca/d) compared to CON; this was observed concomitantly with increased serum and myocardial adiponectin. Diastolic dysfunction was present in WES+DHA rats compared to both WES and CON. Myocyte cross sectional area (CSA) was greater in WES compared to CON rats. In both fat-fed groups, transmission electron microscopy (TEM) revealed myofibril degeneration, disorganized mitochondrial cristae, lipid inclusions and vacuolation. In the absence of hypertension and whole body insulin resistance, WES+DHA intake was associated with more global LV thickening and with diastolic dysfunction, compared to WES feeding alone. Myocyte hypertrophy, possibly related to subcellular injury, is an early change that may contribute to gross hypertrophy. Strain differences in adipokines and myocardial fatty acid accretion may underlie heterogeneous data from rodent studies.
PMCID: PMC3530602  PMID: 23300587
Infection and Immunity  1970;2(3):286-291.
The lipid composition of five parasitic and six saprophytic leptospires was compared. Lipids comprise 18 to 26% of the dry weight of the cells after chloroform-methanol extraction. No residual (bound) lipid was found after acid or alkaline hydrolysis of the extracted residue. The total lipid was composed of 60 to 70% phospholipid, and the remaining lipid was free fatty acids. The phospholipid fraction contained phosphatidylethanolamine as the major component, and phosphatidylglycerol and diphosphatidylglycerol were minor components with traces of lysophatidylethanolamine sometimes found. The major fatty acids of leptospires were hexadecanoic, hexadecenoic, and octadecenoic acids. Both the unusual cis-11-hexadecenoic acid and the more common cis-9-hexadecenoic acid were synthesized by the leptospires. Neither the parasitic nor the saprophytic leptospires can chain elongate fatty acids. However, they were capable of β-oxidation of fatty acids. Both groups of leptospires desaturate fatty acids by an aerobic pathway. When the parasite canicola was cultivated on octadecanoic acid, 87% of the hexadecenoic acid was the 11 isomer, whereas the saprophyte semeranga consisted of 10% of this isomer. In addition, the saprophytic leptospires contained more tetradecanoic acid than the parasites. No differences were observed in the lipid composition of virulent and avirulent strains of canicola.
PMCID: PMC416003  PMID: 16557833
PLoS ONE  2012;7(4):e35072.
H. pylori drug-resistant strains and non-compliance to therapy are the major causes of H. pylori eradication failure. For some bacterial species it has been demonstrated that fatty acids have a growth inhibitory effect. Our main aim was to assess the ability of docosahexaenoic acid (DHA) to inhibit H. pylori growth both in vitro and in a mouse model. The effectiveness of standard therapy (ST) in combination with DHA on H. pylori eradication and recurrence prevention success was also investigated. The effects of DHA on H. pylori growth were analyzed in an in vitro dose-response study and n in vivo model. We analized the ability of H. pylori to colonize mice gastric mucosa following DHA, ST or a combination of both treatments. Our data demonstrate that DHA decreases H. pylori growth in vitro in a dose-dependent manner. Furthermore, DHA inhibits H. pylori gastric colonization in vivo as well as decreases mouse gastric mucosa inflammation. Addition of DHA to ST was also associated with lower H. pylori infection recurrence in the mouse model. In conclusion, DHA is an inhibitor of H. pylori growth and its ability to colonize mouse stomach. DHA treatment is also associated with a lower recurrence of H. pylori infection in combination with ST. These observations pave the way to consider DHA as an adjunct agent in H. pylori eradication treatment.
PMCID: PMC3328494  PMID: 22529974
AMB Express  2012;2:42.
This study explored the influence of various culture conditions on the biomass, lipid content, production of docosahexaenoic acid (DHA), and fatty acid composition of Aurantiochytrium mangrovei strain BL10. The variables examined in this study include the species and concentration of salt, the concentrations of the two substrates glucose and yeast extract, the level of dissolved oxygen, the cerulenin treatment, and the stages of BL10 growth. Our results demonstrate that BL10 culture produces maximum biomass when salinity levels are between 0.2 and 3.0%. Decreasing salinity to 0.1% resulted in a considerable decrease in the biomass, lipid content, DHA production, and DHA to palmitic acid (PA) (DHA/PA) ratio, signifying deterioration in the quality of the oil produced. The addition of 0.9% sodium sulfate to replenish salinity from 0.1% to 1.0% successfully recovered biomass, lipid content and DHA production levels; however, this also led to a decrease in DHA/PA ratio. An increase in oxygen and cerulenin levels resulted in a concomitant decrease in the DHA to docosapentaenoic acid (DPA) (DHA/DPA) ratio in BL10 oil. Furthermore, the DHA/DPA and DHA/PA ratios varied considerably before and after the termination of cell division, which occurred around the 24 hour mark. These results could serve as a foundation for elucidating the biochemistry underlying the accumulation of lipids, and a definition of the extrinsic (environmental or nutritional) and intrinsic (cell growth stage) factors that influence lipid quality and the production of DHA by BL10.
PMCID: PMC3485123  PMID: 22883641
Lipid; Polyunsaturated fatty acid (PUFA); Docosahexaenoic acid (DHA); Aurantiochytrium mangrovei; Thraustochytrid
Nutrients  2010;2(3):355-374.
Long chain fatty acids influence inflammation through a variety of mechanisms; many of these are mediated by, or at least associated with, changes in fatty acid composition of cell membranes. Changes in these compositions can modify membrane fluidity, cell signaling leading to altered gene expression, and the pattern of lipid mediator production. Cell involved in the inflammatory response are typically rich in the n-6 fatty acid arachidonic acid, but the contents of arachidonic acid and of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can be altered through oral administration of EPA and DHA. Eicosanoids produced from arachidonic acid have roles in inflammation. EPA also gives rise to eicosanoids and these often have differing properties from those of arachidonic acid-derived eicosanoids. EPA and DHA give rise to newly discovered resolvins which are anti-inflammatory and inflammation resolving. Increased membrane content of EPA and DHA (and decreased arachidonic acid content) results in a changed pattern of production of eicosanoids and resolvins. Changing the fatty acid composition of cells involved in the inflammatory response also affects production of peptide mediators of inflammation (adhesion molecules, cytokines etc.). Thus, the fatty acid composition of cells involved in the inflammatory response influences their function; the contents of arachidonic acid, EPA and DHA appear to be especially important. The anti-inflammatory effects of marine n-3 PUFAs suggest that they may be useful as therapeutic agents in disorders with an inflammatory component.
PMCID: PMC3257651  PMID: 22254027
leukocyte; neutrophil; macrophage; monocyte; eicosanoid; cytokine; interleukin; fish oil
British Journal of Cancer  1997;75(3):348-353.
We investigated the effects of low-dose eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the incidence and growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in rats fed a high-fat (HF) diet. We also examined the effects of these treatments on the fatty acid composition of tumour and serum. Tumour incidence was significantly decreased by the administration of low-dose EPA and DHA, whereas their inhibitory effects on tumour growth did not reach significance. Serum arachidonic acid (AA) level was decreased by the administration of low-dose EPA and tended to be decreased by the administration of low-dose DHA, whereas tumour AA levels were not changed. The administration of low-dose EPA and DHA may be useful for inhibiting the incidence of breast cancer.
PMCID: PMC2063366  PMID: 9020478
Infection and Immunity  1970;2(5):606-609.
The lipid composition of Treponema pallidum Kazan 5 cultivated in a lipid-defined medium was investigated. Lipids comprised 18 to 20% of the dry weight of the treponeme. Glycolipid and phospholipids accounted for 90 to 95% of the total lipids and free fatty acids made up the remaining 5 to 10%. The major polar lipids were the glycolipid, 1-(O-α-d-galactopyranosyl)-2,3-diglyceride (45 to 55%), and phosphatidylcholine (30 to 40%). Phosphatidylethanolamine (5 to 10%), an unidentified compound (1 to 2%), and occasional trace amounts of diphosphatidylglycerol (cardiolipin) were also found. The monogalactosyldiglyceride was also a major component (50%) of the lipids of the Reiter, Noguchi, and Nichols strains of T. pallidum. The fatty acid composition of Kazan 5 usually consisted of saturated and unsaturated fatty acids ranging from 14 to 18 carbons depending upon the fatty acids added to the culture medium. When the cells were cultivated on elaidic acid (trans-9-octadecenoic acid), their lipids contained only elaidic acid.
PMCID: PMC416057  PMID: 16557884
Barophilic bacteria are microorganisms that grow preferentially (facultative barophiles) or exclusively (obligate barophiles) under elevated hydrostatic pressure. Barophilic bacteria have been isolated from a variety of deep-sea environments. Attempts to characterize these organisms have been hampered by a lack of appropriate methodologies. A colorimetric method for the detection of 19 constitutively expressed enzymes under in situ conditions of pressure and temperature has been devised, using a simple modification of the commercially available API ZYME enzyme assay kit. By using this method, enzyme profiles of 11 barophilic isolates, including an obligate barophile, were determined. Nine of the 10 facultatively barophilic isolates examined exhibited a change of phenotype in at least one enzyme reaction when tested at 1 atm (1 atm = 101.29 kPa), compared with results obtained under in situ pressure. The assay is simple and rapid and allows for direct determination of enzyme activity under conditions of high pressure and low temperature.
PMCID: PMC183426  PMID: 2317048
BMC Genomics  2009;10:110.
Dietary polyunsaturated fatty acids (PUFA), in particular the long chain marine fatty acids docosahexaenoic (DHA) and eicosapentaenoic (EPA), are linked to many health benefits in humans and in animal models. Little is known of the molecular response to DHA and EPA of the small intestine, and the potential contribution of this organ to the beneficial effects of these fatty acids. Here, we assessed gene expression changes induced by DHA and EPA in the wildtype C57BL/6J murine small intestine using whole genome microarrays and functionally characterized the most prominent biological process.
The main biological process affected based on gene expression analysis was lipid metabolism. Fatty acid uptake, peroxisomal and mitochondrial beta-oxidation, and omega-oxidation of fatty acids were all increased. Quantitative real time PCR, and -in a second animal experiment- intestinal fatty acid oxidation measurements confirmed significant gene expression differences and showed in a dose-dependent manner significant changes at biological functional level. Furthermore, no major changes in the expression of lipid metabolism genes were observed in the colon.
We show that marine n-3 fatty acids regulate small intestinal gene expression and increase fatty acid oxidation. Since this organ contributes significantly to whole organism energy use, this effect on the small intestine may well contribute to the beneficial physiological effects of marine PUFAs under conditions that will normally lead to development of obesity, insulin resistance and diabetes.
PMCID: PMC2662879  PMID: 19284886
The Journal of Biological Chemistry  2010;285(29):22027-22035.
Various kinds of fatty acids are distributed in membrane phospholipids in mammalian cells and tissues. The degree of fatty acid unsaturation in membrane phospholipids affects many membrane-associated functions and can be influenced by diet and by altered activities of lipid-metabolizing enzymes such as fatty acid desaturases. However, little is known about how mammalian cells respond to changes in phospholipid fatty acid composition. In this study we showed that stearoyl-CoA desaturase 1 (SCD1) knockdown increased the amount of saturated fatty acids and decreased that of monounsaturated fatty acids in phospholipids without affecting the amount or the composition of free fatty acid and induced unfolded protein response (UPR), evidenced by increased expression of C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78) mRNAs and splicing of Xbox-binding protein 1 (XBP1) mRNA. SCD1 knockdown-induced UPR was rescued by various unsaturated fatty acids and was enhanced by saturated fatty acid. Lysophosphatidylcholine acyltransferase 3 (LPCAT3), which incorporates preferentially polyunsaturated fatty acids into phosphatidylcholine, was up-regulated in SCD1 knockdown cells. Knockdown of LPCAT3 synergistically enhanced UPR with SCD1 knockdown. Finally we showed that palmitic acid-induced UPR was significantly enhanced by LPCAT3 knockdown as well as SCD1 knockdown. These results suggest that a decrease in membrane phospholipid unsaturation induces UPR.
PMCID: PMC2903364  PMID: 20489212
Fatty Acid; Fatty Acid Metabolism; Membrane; Membrane Lipids; Phospholipid; Phospholipid Metabolism; Lipotoxicity; Lysophospholipid Acyltransferase; Unfolded Protein Response
Journal of Bacteriology  1962;84(6):1260-1267.
Marr, Allen G. (University of California, Davis) and John L. Ingraham. Effect of temperature on composition of fatty acids in Escherichia coli. J. Bacteriol. 84:1260–1267. 1962.—Variations in the temperature of growth and in the composition of the medium alter the proportions of individual fatty acids in the lipids of Escherichia coli. As the temperature of growth is lowered, the proportion of unsaturated fatty acids (hexadecenoic and octadecenoic acids) increases. The increase in content of unsaturated acids with a decrease in temperature of growth occurs in both minimal and complex media. Cells harvested in the stationary phase contained large amounts of cyclopropane fatty acids (methylenehexadecanoic and methylene octadecanoic acids) in comparison with cells harvested during exponential growth. Cells grown in a chemostat, limited by the concentration of ammonium salts, show a much higher content of saturated fatty acids (principally palmitic acid) than do cells harvested from an exponentially-growing batch culture in the same medium. Cells grown in a chemostat, limited by the concentration of glucose, show a slightly higher content of unsaturated fatty acids than cells from the corresponding batch culture. The results do not indicate a direct relation between fatty acid composition and minimal growth temperature.
PMCID: PMC278056  PMID: 16561982
PLoS ONE  2010;5(5):e10878.
Beside their health benefits, dietary omega 3 polyunsaturated fatty acids (n-3 PUFA) might impair host resistance to Mycobacterium tuberculosis (Mtb) by creating an immunosuppressive environment. We hypothesized that incorporation of n-3 PUFA suppresses activation of macrophage antimycobacterial responses and favors bacterial growth, in part, by modulating the IFNγ-mediated signaling pathway.
Methodology/Principal Findings
Murine macrophage-like J774A.1 cells were incubated with bovine serum albumin (BSA)-conjugated docosahexaenoic acid (DHA; 22:6n-3) or BSA alone, activated with recombinant IFNγ, and infected with a virulent strain (H37Rv) of M. tuberculosis. The fatty acid composition of macrophage membranes was modified significantly by DHA treatment. DHA-treated macrophages were less effective in controlling intracellular mycobacteria and showed impaired oxidative metabolism and reduced phagolysosome maturation. Incorporation of DHA resulted in defective macrophage activation, as characterized by reduced production of pro-inflammatory cytokines (TNFα, IL-6 and MCP-1), and lower expression of co-stimulatory molecules (CD40 and CD86). DHA treatment impaired STAT1 phosphorylation and colocalization of the IFNγ receptor with lipid rafts, without affecting surface expression of IFNγ receptor.
We conclude that DHA reduces the ability of J774A.1 cells to control M. tuberculosis in response to activation by IFNγ, by modulation of IFNγ receptor signaling and function, suggesting that n-3 PUFA-enriched diets may have a detrimental effect on host immunity to tuberculosis.
PMCID: PMC2878322  PMID: 20526363
Bioactivities of Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA) depend on their chemical forms. The present study was to investigate short term effects of triglyceride (TG), ethyl ester (EE), free fatty acid (FFA) and phospholipid (PL) forms of omega-3 fatty acid (FA) on lipid metabolism in mice, fed high fat or low fat diet.
Male Balb/c mice were fed with 0.7% different Omega-3 fatty acid formulation: DHA bound free fatty acid (DHA-FFA), DHA bound triglyceride (DHA-TG), DHA bound ethyl ester (DHA-EE) and DHA bound phospholipid (DHA-PL) for 1 week, with dietary fat levels at 5% and 22.5%. Serum and hepatic lipid concentrations were analyzed, as well as the fatty acid composition of liver and brain.
At low fat level, serum total cholesterol (TC) level in mice fed diets with DHA-FFA, DHA-EE and DHA-PL were significantly lower than that in the control group (P < 0.05). Hepatic TG level decreased significantly in mice fed diets with DHA-TG (P < 0.05), DHA-EE (P < 0.05) and DHA-PL (P < 0.05), while TC level in liver was significantly lower in mice fed diets with TG and EE compared with the control group (P < 0.05). At high fat level, mice fed diets with DHA-EE and DHA-PL had significantly lower hepatic TC level compared with the control diet (P < 0.05). Hepatic PL concentration experienced a significant increase in mice fed the diet with PL at high fat level (P < 0.05). Furthermore, both at low and high fat levels, hepatic DHA level significantly increased and AA level significantly decreased in all forms of DHA groups (P < 0.05), compared to control groups at two different fat levels, respectively. Additionally, cerebral DHA level in mice fed diets with DHA-FFA, DHA-EE and DHA-PL significantly increased compared with the control at high fat level (P < 0.05), but no significant differences were observed among dietary treatments for mice fed diets with low fat level.
The present study suggested that not only total dietary fat content but also the molecular forms of omega-3 fatty acids contributed to lipid metabolism in mice. DHA-PL showed effective bioactivity in decreasing hepatic and serum TC, TG levels and increasing omega-3 concentration in liver and brain.
PMCID: PMC3393618  PMID: 22676394
Omega-3 fatty acid; DHA; EPA; Lipid metabolism; Triglycerides; Ethyl ester; Phospholipids
Journal of Clinical Investigation  1972;51(2):338-344.
To study certain membrane repair processes in human erythrocytes, vitamin E-deficient cells were incubated with hydrogen peroxide. The incorporation of exogenous fatty acid and the transfer of fatty acid from phosphatidylcholine and neutral lipid into phosphatidylethanolamine were examined using radioactive fatty acids.
Hydrogen peroxide stimulated the incorporation of fatty acid into all membrane phospholipids. The specific activity of phosphatidylethanolamine was increased disproportionately.
The lipids of the membranes of erythrocytes were labeled with saturated and unsaturated fatty acid. When these erythrocytes were subsequently incubated with hydrogen peroxide, both types of fatty acid were transferred from superficial erythrocyte neutral lipids into phosphatidylethanolamine. However, the unsaturated fatty acids of phosphatidylethanolamine were subsequently altered by hydrogen peroxide, whereas the saturated fatty acids were not. The cumulative effect of these processes was a relative decrease in unsaturated fatty acid and an increase in saturated fatty acid in the phosphatidylethanolamine of the erythrocyte membrane.
The net effect of these events represents the operation of repair processes which distort the usual fatty acid composition of erythrocyte membranes in the presence of H2O2. This distortion may contribute to membrane permeability changes which occur during peroxide exposure and which precede the eventual hemolysis of these cells.
PMCID: PMC302132  PMID: 5009118
British Journal of Cancer  1997;75(5):650-655.
Unsaturated fatty acids, including n-3 polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (C22:6, DHA) and eicosapentaenoic acid (C20:5, EPA), and a series of n-6 PUFAs were investigated for their anti-tumour and antimetastatic effects in a subcutaneous (s.c.) implanted highly metastatic colon carcinoma 26 (Co 26Lu) model. EPA and DHA exerted significant inhibitory effects on tumour growth at the implantation site and significantly decreased the numbers of lung metastatic nodules. Oleic acid also significantly inhibited lung metastatic nodules. Treatment with arachidonic acid showed a tendency for reduction in colonization. However, treatment with high doses of fatty acids, especially linoleic acid, increased the numbers of lung metastatic nodules. DHA and EPA only inhibited lung colonizations when administered together with the tumour cells, suggesting that their incorporation is necessary for an influence to be exerted. Chromatography confirmed that contents of fatty acids in both tumour tissues and plasma were indeed affected by the treatments. Tumour cells pretreated with fatty acids in vivo, in particular DHA, also showed a low potential for lung colony formation when transferred to new hosts. Thus, DHA treatment exerted marked antimetastatic activity associated with pronounced change in the fatty acid component of tumour cells. The results indicate that uptake of DHA into tumour cells results in altered tumour cell membrane characteristics and a decreased ability to metastasize.
PMCID: PMC2063338  PMID: 9043019
Journal of Bacteriology  1986;167(3):986-991.
During the progression of Mycoplasma capricolum cultures from the early exponential to the stationary phase of growth, a decrease in the phospholipid-to-protein ratio and increases in both the unsaturated-to-saturated fatty acid ratio and the diphosphatidylglycerol (DPG)-to-phosphatidylglycerol (PG) ratio were found. The freedom of motion of spin-labeled fatty acids incorporated into the membrane remained unchanged throughout the growth cycle. The increase in DPG was almost stoichiometric with the decrease in PG. Furthermore, exogenous PG added to the medium was incorporated by the cells and partially converted to DPG. The DPG that was accumulated upon aging was always more unsaturated than the PG. This accumulation was enhanced in palmitic acid-poor media, but was inhibited even in aged cells when the cells were grown in palmitic acid-rich media, suggesting that the accumulation of DPG upon aging was associated with changes in the fatty acid composition of membrane lipids rather than with the transition of the cells from the exponential- to stationary-growth phase.
PMCID: PMC215969  PMID: 3745126

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