De Novo Lipogenesis and Stearoyl-CoA Desaturase Are Coordinately Regulated in the Human Adipocyte and Protect against Palmitate-induced Cell Injury

De novo lipogenesis (DNL) is paradoxically up-regulated by its end product, saturated fatty acids (SAFAs). We tested the hypothesis that SAFA-induced up-regulation of DNL reflects coordinate up-regulation of elongation and desaturation pathways for disposal of SAFAs and production of monounsaturated fatty acids to protect cells from SAFA toxicity. Human preadipocytes were differentiated in vitro for 14 days with [U-¹³C]palmitate (0–200 μm) to distinguish exogenous fatty acids from those synthesized by DNL. Exogenous palmitate up-regulated DNL (p < 0.001) concomitantly with SCD and elongation (each p < 0.001). Adipocytes from some donors were intolerant to high palmitate concentrations (400 μm). Palmitate-intolerant cells showed lower TG accumulation. They had lower expression of SCD mRNA and less monounsaturated fatty acids in TG, emphasizing the importance of desaturation for dealing with exogenous SAFAs. There was greater [U-¹³C]palmitate incorporation in phospholipids. SCD knockdown with small interfering RNA caused down-regulation of DNL and of expression of DNL-related genes, with reduced membrane fluidity (p < 0.02) and insulin sensitivity (p < 0.01), compared with scrambled small interfering RNA controls. There was preferential channeling of DNL-derived versus exogenous palmitate into elongation and of DNL-derived versus exogenous stearate into desaturation. DNL may not act primarily to increase fat stores but may serve as a key regulator, in tandem with elongation and desaturation, to maintain cell membrane fluidity and insulin sensitivity within the human adipocyte.     

Dietary conjugated linoleic acid alters long chain polyunsaturated fatty acid metabolism in brain and liver of neonatal pigs

Effects of dietary conjugated linoleic acid (CLA, 1% mixed isomers) on n-6 long-chain polyunsaturated fatty acid (LCPUFA) oxidation and biosynthesis were investigated in liver and brain tissues of neonatal piglets. Fatty acid β-oxidation was measured in tissue homogenates using [1-¹⁴C]linoleic acid (LA) and -arachidonic acid (ARA) substrates, while fatty acid desaturation and elongation were traced using [U-¹³C]LA and GC-MS. Dietary CLA had no effect on fatty acid β-oxidation, but significantly decreased n-6 LCPUFA biosynthesis by inhibition of LA elongation and desaturation. Differences were noted between our ¹³C tracer assessment of desaturation/elongation and simple precursor-product indices computed from fatty acid composition data, indicating that caution should be exercised when employing the later. The inhibitory effects of CLA on elongation/desaturation were more pronounced in pigs fed a low fat diet (3% fat) than a high fat diet (25% fat). Direct elongation of linoleic acid to C20:2n-6 via the alternate elongation pathway might play an important role in n-6 LCPUFA synthesis because more than 40% of the synthetic products of [U-¹³C]LA accumulated in [¹³C]20:2n-6. Overall, the data show that dietary CLA shifted the distribution of the synthetic products of [U-¹³C]LA between elongation and desaturation in liver and decreased the total synthetic products of [U-¹³C]LA in brain by inhibiting LA elongation to C20:2n-6. The impact of CLA on brain LCPUFA metabolism of the developing neonate merits consideration and further investigation.     

多不饱和脂肪酸合成途径研究进展

多不饱和脂肪酸在大多数生物体膜生物学和信号传递过程中起着至关重要的作用。最近研究发现,一些深海生物合成多不饱和脂肪酸并非由饱和脂肪酸的延长及脱饱和反应,而是由聚酮合酶途径(polyketide synthase,PKS)直接合成。介绍多不饱和脂肪酸的生物合成并总结近年来聚酮合酶这一新途径及其分子机制的研究进展。     

Fatty acid metabolism in Atlantic salmon (Salmo salar L.) hepatocytes and influence of dietary vegetable oil

Isolated hepatocytes from Atlantic salmon (Salmo salar), fed diets containing either 100% fish oil or a vegetable oil blend replacing 75% of the fish oil, were incubated with a range of seven (14)C-labelled fatty acids. The fatty acids were [1-(14)C]16:0, [1-(14)C]18:1n-9, 91-(14)C]18:2n-6, [1-(14)C]18:3n-3, [1-(14)C]20:4n-6, [1-(14)C]20:5n-3, and [1-(14)C]22:6n-3. After 2 h of incubation, the hepatocytes and medium were analysed for acid soluble products, incorporation into lipid classes, and hepatocytes for desaturation and elongation. Uptake into hepatocytes was highest with [1-(14)C]18:2n-6 and [1-(14)C]20:5n-3 and lowest with [1-(14)C]16:0. The highest recovery of radioactivity in the cells was found in triacylglycerols. Of the phospholipids, the highest recovery was found in phosphatidylcholine, with [1-(14)C]16:0 and [1-(14)C]22:6n-3 being the most prominent fatty acids. The rates of beta-oxidation were as follows: 20:4n-6>18:2n-6=16:0>18:1n-9>22:6n-3=18:3n-3=20:5n-3. Of the fatty acids taken up by the hepatocytes, [1-(14)C]16:0 and [1-(14)C]18:1n-9 were subsequently exported the most, with the majority of radioactivity recovered in phospholipids and triacylglycerols, respectively. The major products from desaturation and elongation were generally one cycle of elongation of the fatty acids. Diet had a clear effect on the overall lipid metabolism, with replacing 75% of the fish oil with vegetable oil resulting in decreased uptake of all fatty acids and reduced incorporation of fatty acids into cellular lipids, but increased beta-oxidation activity and higher recovery in products of desaturation and elongation of [1-(14)C]18:2n-6 and [1-(14)C]18:3n-3.     

Effects of dietary fish oil substitution by Echium oil on enterocyte and hepatocyte lipid metabolism of gilthead seabream (Sparus aurata L.)

The fatty acid profile of vegetable oils (VOs), together with the poor ability of marine fish to convert polyunsaturated fatty acids (PUFA) to highly unsaturated fatty acids (HUFA), lead to important changes in the nutritional value of farmed fish fed VO, which include increased fat and 18:2n-6 and reduced n-3 HUFA. Echium oil (EO) has a good n-3/n-6 balance as well as an interesting profile with its high content of unusual fatty acids (SDA, 18:4n-3 and GLA, 18:3n-6) that are of increasing pharmacological interest. The effects of substituting 50 % of dietary fish oil (FO) by EO on gilthead seabream (Sparus aurata L.) enterocyte and hepatocyte lipid metabolism were studied. After 4 months of feeding, cell viability, total lipid contents and lipid class compositions were not affected by EO. The cells clearly reflected the fatty acid profile of the EO showing increased SDA, GLA and its elongation product 20:3n-6, and only minorly decreased n-3 HUFA compared to other VO. Metabolism of [1-¹⁴C]18:2n-6 and [1-¹⁴C]18:3n-3 was also unaffected by EO in terms of total uptake, incorporation, β-oxidation and elongation–desaturation activities.     

Upregulated mRNA expression of desaturase and elongase,two enzymes involved in highly unsaturated fatty acids biosynthesis pathways during follicle maturation in zebrafish

Background  

Although unsaturated fatty acids such as eicosapentaenoic acid (EPA, C20:5n-3), docosahexaenoic acid (DHA, C22:6n-3) and arachidonic acid (ARA, C20:4n-6), collectively known as the highly unsaturated fatty acids (HUFA), play pivotal roles in vertebrate reproduction, very little is known about their synthesis in the ovary. The zebrafish (Danio rerio) display capability to synthesize all three HUFA via pathways involving desaturation and elongation of two precursors, the linoleic acid (LA, C18:2n-6) and linolenic acid (LNA, C18:3n-3). As a prerequisite to gain full understanding on the importance and regulation of ovarian HUFA synthesis, we described here the mRNA expression pattern of two enzymes; desaturase (fadsd6) and elongase (elovl5), involved in HUFA biosynthesis pathway, in different zebrafish ovarian follicle stages. Concurrently, the fatty acid profile of each follicle stage was also analyzed.     

Palmitic acid (16:0) competes with omega-6 linoleic and omega-3 ɑ-linolenic acids for FADS2 mediated Δ6-desaturation

Sapienic acid, 16:1n-10 is the most abundant unsaturated fatty acid on human skin where its synthesis is mediated by FADS2 in the sebaceous glands. The FADS2 product introduces a double bond at the Δ6, Δ4 and Δ8 positions by acting on at least ten substrates, including 16:0, 18:2n-6, and 18:3n-3. Our aim was to characterize the competition for accessing FADS2 mediated Δ6 desaturation between 16:0 and the most abundant polyunsaturated fatty acids (PUFA) in the human diet, 18:2n-6 and 18:3n-3, to evaluate whether competition may be relevant in other tissues and thus linked to metabolic abnormalities associated with FADS2 or fatty acid levels. MCF7 cells stably transformed with FADS2 biosynthesize 16:1n-10 from exogenous 16:0 in preference to 16:1n-7, the immediate product of SCD highly expressed in cancer cell lines, and 16:1n-9 via partial β-oxidation of 18:1n-9. Increasing availability of 18:2n-6 or 18:3n-3 resulted in decreased bioconversion of 16:0 to 16:1n-10, simultaneously increasing the levels of highly unsaturated products. FADS2 cells accumulate the desaturation-elongation products 20:3n-6 and 20:4n-3 in preference to the immediate desaturation products 18:3n-6 and 18:4n-3 implying prompt/coupled elongation of the nascent desaturation products. MCF7 cells incorporate newly synthesized 16:1n-10 into phospholipids. These data suggest that excess 16:0 due to, for instance, de novo lipogenesis from high carbohydrate or alcohol consumption, inhibits synthesis of highly unsaturated fatty acids, and may in part explain why supplemental preformed EPA and DHA in some studies improves insulin resistance and other factors related to diabetes and metabolic syndrome aggravated by excess calorie consumption.     

Dietary fatty acids and cardiovascular disease: an epidemiological approach

The quality of dietary fat in relation to cardiovascular disease forms the basis of the diet-heart hypothesis. Current recommendations on dietary fat now emphasise quality rather than quantity. The focus of this review is to summarise the results from prospective cohort studies on dietary fat and cardiovascular disease outcomes. Relatively few prospective cohort studies have found an association between dietary fat quality and cardiovascular disease, partly because of limitations in estimating dietary intake. Saturated and trans fatty acids have increased cardiovascular risk in several studies. Both n-6 and n-3 polyunsaturated fatty acids have been associated with lower cardiovascular risk. Within the n-6 series, linoleic acid seems to decrease cardiovascular risk. Within the n-3 series the long-chain fatty acids (eicosapentaenoic and docosahexaenoic acids) are associated with decreased risk for especially fatal coronary outcomes, whereas the role of alpha-linolenic acid is less clear. Dietary fat quality also influences the activity of enzymes involved in the desaturation of fatty acids in the body. Serum desaturase indices have been consistently associated with adverse cardiovascular outcomes. Data from metabolic and clinical studies reinforce findings from observational studies supporting recommendations to replace saturated and trans fat with unsaturated fat in the prevention of cardiovascular disease.     

Effect of grazing pastures with different botanical composition by lambs on rumen fatty acid metabolism and fatty acid pattern of longissimus muscle and subcutaneous fat

In order to study the effect of grazing pastures with a different botanical composition on rumen and intramuscular fatty acid metabolism, 21 male lambs were assigned to three botanically different pastures: botanically diverse (BD) (consisting for 65% of a variety of grass species); Leguminosa rich (L) (consisting for 61% of Leguminosae) and intensive English ryegrass (IR) (with 69% Lolium perenne). Pastures were sampled weekly for 12 weeks for analysis of their fatty acid content and composition and on nine occasions to determine the botanical composition. Ruminal and abomasal contents were sampled at slaughter and muscle and subcutaneous fat 24 h after slaughter. All samples were prepared and analysed for fatty acid composition. The L pasture showed a higher fatty acid content (29.8 mg/g dry matter (DM) v. 18.5 and 25.5 mg/g DM, for BD and IR pastures, respectively), but the sum of the proportions of the major polyunsaturated fatty acids, C18:2 n-6 and C18:3 n-3, were similar for the three pastures (69.9, 69.4 and 71.1% of fatty acids methyl esters (FAME) for BD, L and IR pastures, respectively). The BD pasture was richer in C18:2 n-6 (18.2% of FAME), while IR pasture had a higher C18:3 n-3 content (57.2% of FAME). Rumen data showed that animals grazing the BD pasture presented higher proportions of biohydrogenation intermediates, mainly C18:1 t11, C18:2 t11c15 and CLA c9t11, suggesting an inhibition of biohydrogenation. These changes were associated with shifts in the rumen microbial population as indicated by differences in the rumen pattern of volatile fatty acids, microbial odd- and branched-chain fatty acids. In L pasture animals, the content of C18:2 n-6 and C18:3 n-3 in the abomasum and subcutaneous fat was higher. Finally, higher proportions of C20:4 n-6, C20:5 n-3 and C22:5 n-3 and higher indices for elongation and desaturation activity in the intramuscular fat of BD grazing animals suggest some stimulation of elongation and desaturation of long-chain fatty acids, although this also might have been provoked partially by reduced fat deposition (due to a lower growth rate of the animals).     

Regulation of n-3 and n-6 Fatty Acid Metabolism in Retinal and Cerebral Microvascular Endothelial Cells by High Glucose

Abstract: The present study was undertaken to determine whether polyunsaturated fatty acid metabolism is affected by high glucose levels in cerebral and retinal microvascular endothelial cells. The metabolism of [3-¹⁴C]22:5n-3 and [1-¹⁴C]18:2n-6 was studied in cells previously cultured for 5 days in normal (5 m M ) or high (30 m M ) glucose medium. After incubation of retinal endothelial cells with [3-¹⁴C]22:5n-3 in the high glucose condition, the formation of labeled 24:6n-3 and 22:6n-3 was increased, and that of labeled 24:5n-3 was decreased, compared with the normal glucose condition. The changes were found for fatty acids esterified in cellular lipids and those released into the medium. After incubation with [1-¹⁴C]18:2n-6, levels of all elongation/desaturation products were increased at the expense of the precursor in retinal endothelial cells cultured in high glucose medium. The changes were primarily found for esterified fatty acids, with the release of n-6 fatty acids being minor in both glucose concentrations. By contrast, high glucose levels did not affect the metabolism of [3-¹⁴C]22:5n-3 and [1-¹⁴C]18:2n-6 in cerebral endothelial cells. The changes in metabolic activity of retinal endothelial cells were not reflected in the fatty acid composition. The present data suggest that high glucose can increase the desaturation process in retinal but not cerebral endothelial cells. This may produce some lipid abnormalities in retinal microvasculature and contribute to altered vascular function observed in diabetic retinopathy.     

Metabolism of hexacosatetraenoic acid (C26:4,n-6) in immature rat brain.

Rat brain was recently found to contain polyenoic very-long-chain fatty acids (VLCFA) belonging to the n-3 and n-6 series with four, five and six double bonds and even-carbon chain lengths from 24 to 38 [Robinson, Johnson & Poulos (1990) Biochem. J. 265, 763-767]. In the present paper, the metabolism in vivo of hexacosatetraenoic acid (C26:4,n-6) was studied in neonatal rat brain. Rats were injected intracerebrally with [1-14C]C26:4,n-6 and the labelled metabolites were examined after 4 h. Radioactivity was detected mainly in non-esterified fatty acids, with smaller amounts in other neutral lipids and phospholipids. Radiolabelled fatty acid products included C28-36 tetraenoic and C26-28 pentaenoic VLCFA formed by elongation and desaturation of the substrate, and C14-24 saturated, C16-24 monoenoic, C18-24 dienoic, C18-22 trienoic and C20-24 tetraenoic fatty acids formed from released [1-14C]acetate either by synthesis de novo or by elongation of endogenous fatty acids. The data suggest that polyenoic VLCFA are synthesized in brain from shorter-chain precursor fatty acids and undergo beta-oxidation.     

The effects of 2-bromopalmitate on the fatty acid composition in differentiating adipocytes of red sea bream (Pagrus major)

To determine whether external factors affect the adipogenic function of fish adipocytes, the effects of 2-bromopalmitate (a PPAR agonist) on the fatty acid composition in differentiating adipocytes of red sea bream were investigated in vitro. In the presence of 2-bromopalmitate, the red sea bream adipocytes were differentiated and the effects on the fatty acid composition and the adipogenic gene expression were analyzed. With the level of 2-bromopalmitate, the content of 16:1n-7, a delta-9 desaturation product, increased in association with the increase in a stearoyl CoA desaturase (SCD) gene expression level while the triglyceride accumulation was not affected. Subsequently, the effects on the bioconversion of the n-3 and n-6 fatty acids, which are main series of dietary essential fatty acids, were examined. In the presence of 300 μM of 18:3n-3 or 18:2n-6, red sea bream stromal-vascular cells accumulated the lipid in the cytoplasm within 3 days by the fatty acid uptake with the increase of corresponding fatty acid contents. Furthermore, in both the 18:3n-3 and 18:2n-6 stored cells, the products of delta-6 desaturation (18:4n-3 and 18:3n-6, respectively) and C_18–20 elongation (20:3n-3 and 20:2n-6, respectively) were detected. However, neither the delta-6 desatutration nor C_18–20 elongation of 18:3n-3 and 18:2n-6 were enhanced by 2-bromopalmitate treatment. In conclusion, the results indicate that the adipocyte function in fish, e.g. adipogenic gene expression and fatty acid composition, can be modified by external factors and a main effect of 2-bromopalmitate is the increase in the content of delta-9 desaturation product by stimulating the SCD gene expression.     

Hydrogen isotopic fractionations during desaturation and elongation associated with polyunsaturated fatty acid biosynthesis in marine macroalgae

Compound-specific hydrogen isotopic compositions (deltaD) of saturated, monounsaturated and polyunsaturated fatty acids have been determined for natural marine macroalgae including two brown algae (Heterokontophyta) and two red algae (Rhodophyta). deltaD values of individual fatty acids from four macroalgae exhibit a wide variation ranging from -189% to +48%. Generally, stearic (18:0), arachidic (20:0) and behenic acids (22:0) are much more enriched in D by up to approximately 180% relative to myristic (14:0), palmitic (16:0), octatetraenoic [18:4(n-3)] and eicosapentaenoic acids [20:5(n-3)]. Other fatty acids such as oleic [18:1(n-9)], lenoleic [18:2(n-6)] and linolenic acids [18:3(n - 3)] fall isotopically between these fatty acids. This wide deltaD variation of fatty acids is probably explained by the hydrogen isotopic fractionation during desaturation being much larger than that during elongation in the network of polyunsaturated fatty acid biosynthesis. A large hydrogen isotopic fractionation during desaturation may cause D-enrichment in the remaining hydrogen of the residual fatty acids, which could be controlled by the relative flux into their desaturates.     

Phospholipid and triacylglycerol fatty acid composition of major life stages of sunn pest,Eurygaster integriceps (Heteroptera: Scutelleridae)

Phospholipid and triacylglycerol fatty acid compositions of whole animals from all life stages of Eurygaster integriceps, including eggs, nymphs, pre-diapausing adults and diapausing adults, were determined. The fatty acid composition of total lipids of their food, wheat, was also determined. The major components of the insects and their food were the expected C16 and C18 saturated and unsaturated fatty acids. Since fatty acid compositions of third-stadium nymphs were not similar to the profiles of their food, most likely, dietary fatty acids are modified by the insect. The fact is that the food does not provide C20 polyunsaturated fatty acids, but the insect tissue lipids include these components. We suggest biosynthesis of the C20 components by elongation/desaturation of C18:2n-6, an abundant component of the diets. We also show differences in fatty acid profiles from each of the life stages.     

Fatty acid-related modulations of membrane fluidity in cells: detection and implications

Abstract

Metabolic homeostasis of fatty acids is complex and well-regulated in all organisms. The biosynthesis of saturated fatty acids (SFA) in mammals provides substrates for β-oxidation and ATP production. Monounsaturated fatty acids (MUFA) are products of desaturases that introduce a methylene group in cis geometry in SFA. Polyunsaturated fatty acids (n-6 and n-3 PUFA) are products of elongation and desaturation of the essential linoleic acid and α-linolenic acid, respectively. The liver processes dietary fatty acids and exports them in lipoproteins for distribution and storage in peripheral tissues. The three types of fatty acids are integrated in membrane phospholipids and determine their biophysical properties and functions. This study was aimed at investigating effects of fatty acids on membrane biophysical properties under varying nutritional and pathological conditions, by integrating lipidomic analysis of membrane phospholipids with functional two-photon microscopy (fTPM) of cellular membranes. This approach was applied to two case studies: first, pancreatic beta-cells, to investigate hormetic and detrimental effects of lipids. Second, red blood cells extracted from a genetic mouse model defective in lipoproteins, to understand the role of lipids in hepatic diseases and metabolic syndrome and their effect on circulating cells.     

Incorporation into phospholipid classes and metabolism via desaturation and elongation of various 14C-labelled (n-3) and (n-6) polyunsaturated fatty acids in trout astrocytes in primary culture

The incorporation and metabolism of [1-14C]18:3(n-3), [1-14C]20:5(n-3), [1-14C]18:2(n-6), and [1-14C]20:4(n-6) were studied in primary cultures of trout brain astrocytes. There were no significant differences between the amounts of individual fatty acids incorporated into total lipid at 22 degrees C, with greater than 90% of all the fatty acids being incorporated into polar lipid classes. The distributions of 18:2(n-6), 18:3(n-3), and 20:5(n-3) in individual phospholipid classes at 22 degrees C were very similar, with 57-63 and 18-24% being incorporated into phosphatidylcholine and phosphatidylethanolamine, respectively. Approximately equal amounts of 20:4(n-6), approximately 30% of the total, were incorporated into each of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol. The metabolism of the (n-3) fatty acids to longer-chain and more unsaturated species was significantly greater than that of (n-6) acids, but delta 4-desaturase activity was very low. A culture temperature of 10 degrees C increased the incorporation of all the fatty acids into total lipid and that of C20 fatty acids into polar lipid. At 10 degrees C, the incorporation of C20 fatty acids into phosphatidylethanolamine and phosphatidylinositol was increased, and the incorporation into phosphatidylcholine and phosphatidylserine was decreased. The distribution of C18 fatty acids was unchanged at the lower temperature, as was the desaturation and elongation of all the polyunsaturated fatty acids incorporated.     

Dietary myristic acid at physiologically relevant levels increases the tissue content of C20:5 n-3 and C20:3 n-6 in the rat

This study was designed to investigate the effect of myristic acid on the biosynthesis and metabolism of highly unsaturated fatty acids, when it is supplied in a narrow physiological range in the diet of the rat (0.2-1.2% of total dietary energy). Three experimental diets were designed, containing 22% of total dietary energy as lipids and increasing doses of myristic acid (0.71, 3.00 and 5.57% of total fatty acids). Saturated fat did not exceed 31% of total fat and the C18:3 n-3 amount in each diet was strictly equal (1.6% of total fatty acids). After 7 weeks, the diets had no effect on plasma cholesterol level but greatly modified the liver, plasma and adipose tissue saturated, monounsaturated and polyunsaturated fatty acid profiles. Firstly, daily intakes of myristic acid resulted in a dose-dependent tissue accumulation of myristic acid itself. Palmitic acid was significantly increased in the tissues of the rats fed the higher dose of myristic acid. A dose-response accumulation of tissue C16:1 n-7 as a function of dietary C14:0 was also shown. Secondly, a main finding was that, among n-3 and n-6 polyunsaturated fatty acids, a dose-response accumulation of liver and plasma C20:5 n-3 and C20:3 n-6 (two precursors of eicosanoids) as a function of dietary C14:0 was shown. This result suggests that dietary myristic acid may participate in the regulation of highly unsaturated fatty acid biosynthesis and metabolism.     

Cellular energy metabolism during fetal development. V. Fatty acid synthesis by the developing heart

We have investigated fatty acid synthesis by the developing heart. The only system for fatty acid synthesis in the heart is the mitochondrial elongation pathway. Myocardial fatty acid elongation was very low prenatally but increased rapidly during the first week of life. Coincident with weaning there was a sharp drop in elongation activity possibly related to a shift from the high fat intake provided by the milk to the carbohydrate diet provided by standard laboratory chow. Either NADH or NADPH could provide reducing equivalents for myocardial fatty acid elongation. The presence of a long-chain fatty acid primer in the medium resulted in a higher incorporation of acetyl-CoA throughout the developmental period. However, the ratio of endogenous fatty acid elongation activity to that in the presence of an added primer increased with age presumably in relation to the postnatal increase in the availability of long-chain fatty acid primers. Products of fatty acid elongation in postnatal rats included a range of saturated and unsaturated fatty acids with major peaks of stearic acid (18:0) and 20- and 22-carbon unsaturated fatty acids suggesting elongation of the palmityl-CoA primer by the-two carbon units of acetyl-CoA. Decarboxylation of fatty acid products indicated that all synthesis could be accounted for by chain elongation. The observed developmental changes in myocardial fatty acid elongation may be related to functional, structural, and nutritional adaptations of the cell to the postnatal environment.     

Associations of Erythrocyte Fatty Acids in the De Novo Lipogenesis Pathway with Proxies of Liver Fat Accumulation in the EPIC-Potsdam Study

BackgroundBiomarker fatty acids (FAs) reflecting de novo lipogenesis (DNL) are strongly linked to the risk of cardiometabolic diseases. Liver fat accumulation could mediate this relation. There is very limited data from human population-based studies that have examined this relation.ObjectiveThe aim of this study was to investigate the relation between specific FAs in the DNL pathway and liver fat accumulation in a large population-based study.MethodsWe conducted a cross-sectional analysis of a subsample (n = 1,562) of the EPIC-Potsdam study, which involves 27,548 middle-aged men and women. Baseline blood samples have been analyzed for proportions of 32 FAs in erythrocyte membranes (determined by gas chromatography) and biomarker concentrations in plasma. As indicators for DNL, the DNL-index (16:0 / 18:2n-6) and proportions of individual blood FAs in the DNL pathway were used. Plasma parameters associated with liver fat content (fetuin-A, ALT, and GGT) and the algorithm-based fatty liver index (FLI) were used to reflect liver fat accumulation.ResultsThe DNL-index tended to be positively associated with the FLI and was positively associated with GGT activity in men (p for trend: 0.12 and 0.003). Proportions of 14:0 and 16:0 in erythrocytes were positively associated with fetuin-A, whereas 16:1n-7 were positively associated with the FLI and GGT activity (all p for trends in both sexes at least 0.004). Furthermore, the proportion of 16:1n-7 was positively related to fetuin-A in women and ALT activity in men (all p for trend at least 0.03). The proportion of 16:1n-9 showed positive associations with the FLI and GGT activity in men and fetuin-A in both sexes, whereas 18:1n-7 was positively associated with GGT activity in men (all p for trend at least 0.048).ConclusionFindings from this large epidemiological study suggest that liver fat accumulation could link erythrocyte FAs in the DNL pathway to the risk of cardiometabolic diseases.     

Metabolism of linoleic and α-linolenic acids in cultured cardiomyocytes: Effect of different N-6 and N-3 fatty acid supplementation

The metabolites of linoleic (LA) and -linolenic (ALA) acids are involved in coronary heart disease. Both n-6 and n-3 essential fatty acids (EFAs) are likely to be important in prevention of atherosclerosis since the common risk factors are associated with their reduced 6-desaturation. We previously demonstrated the ability of heart tissue to desaturate LA. In this study we examined the ability of cultured cardiomyocytes to metabolize both LA and ALA in vivo, in the absence and in the presence of gamma linolenic acid (GLA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) alone or combined together. In control conditions, about 25% of LA and about 90% of ALA were converted in PUFAs. GLA supplementation had no influence on LA conversion to more unsaturated fatty acids, while the addition of n-3 fatty acids, alone or combined together, significantly decreased the formation of interconversion products from LA. Using the combination of n-6 and n-3 PUFAs, GLA seemed to counterbalance partially the inhibitory effect of EPA and DHA on LA desaturation/elongation. The conversion of ALA to more unsaturated metabolites was greatly affected by GLA supplementation. Each supplemented fatty acid was incorporated to a significant extent into cardiomyocyte lipids, as revealed by gas chromatographic analysis. The n-6/n-3 fatty acid ratio was greatly influenced by the different supplementations; the ratio in GLA+EPA+DHA supplemented cardiomyocytes was the most similar to that recorded in control cardiomyocytes. Since important risk factors for coronary disease may be associated with reduced 6-desaturation of the parent EFAs, administration of n-6 or n-3 EFA metabolites alone could cause undesirable effects. Since they appear to have different and synergistic roles, only combined treatment with both n-6 and n-3 metabolites is likely to achieve optimum results.