Anke Jaudszus

Fatty acid distribution of cord and maternal blood in human pregnancy: special focus on individual trans fatty acids and conjugated linoleic acids

BackgroundMaternal nutrition in pregnancy has a crucial impact on the development of the fetus. Dietary trans fatty acids (t FA) are known to have adverse health effects, especially during pregnancy. However, the distribution of t FA produced via partial hydrogenation of vegetable oils (mainly elaidic acid; t 9) differs compared to ruminant-derived t FA (mainly vaccenic acid; t 11). Recent findings indicate that they may have different impact on human health.Therefore, in this study, plasma and erythrocytes of mother-child pairs (n = 55) were sampled to investigate the distribution of t FA, including individual trans C18:1 fatty acids and conjugated linoleic acids (CLA) in fetal related to maternal lipids; with additional consideration of maternal dairy fat intake.ResultsPortion of t 9 and t 11, but also of c 9,t 11 CLA was higher in maternal than in fetal blood lipids. The portion of t 9 in maternal and fetal lipids differed only slightly. In contrast, the portion of fetal t 11 was only half of that in maternal blood. This led to a fetal t 9/t 11-index in plasma and erythrocytes being twice as high compared to the maternal values. A high dairy fat intake resulted in elevated portions of t 11 and its Δ9-desaturation product c 9,t 11 CLA in maternal blood. In contrast, in the respective fetal blood lipids only c 9,t 11 CLA, but not t 11 was increased. Nevertheless, a positive association between maternal and fetal plasma exists for both t 11 and c 9,t 11 CLA. Furthermore, in contrast to t 9, t 11 was not negatively associated with n-3 LC-PUFA in fetal blood lipids.ConclusionsFetal blood fatty acid composition essentially depends on and is altered by the maternal fatty acid supply. However, in addition to dietary factors, other aspects also contribute to the individual fatty acid distribution (oxidation, conversion, incorporation). The lower portion of fetal t 11 compared to maternal t 11, possibly results from Δ9-desaturation to c 9,t 11 CLA and/or oxidation. Based on the fatty acid distribution, it can be concluded that t 11 differs from t 9 regarding its metabolism and their impact on fetal LC-PUFA.

trans Palmitoleic acid arises endogenously from dietary vaccenic acid

BACKGROUND trans Palmitoleic acid (t-16:1n-7, or 16:1 t9 in the δ nomenclature usually applied to trans fatty acids and used herein) arouses great scientific interest because it has been suggested to serve as a biomarker for lower risks of type 2 diabetes and coronary artery disease. OBJECTIVE Although 16:1 t9 has been assumed to derive from dietary sources, we examined the hypothesis that 16:1 t9 might also be endogenously produced from its metabolic precursor vaccenic acid (t-18:1n-7 or 18:1 t11). DESIGN We reevaluated fatty acid data obtained from one human intervention study and one cellular model in both of which 18:1 t11 was supplemented. Both studies have already been published, but to our knowledge, 16:1 t9 has not yet been considered. This reanalysis of the datasets was reasonable because a new methodology for identifying 16:1 cis and trans isomers allowed us to address the subject presented in this article. RESULTS Data showed that the systemic or intracellular increase in 16:1 t9 was strongly correlated with the increase in 18:1 t11 after the dietary intake or cellular uptake of 18:1 t11. The conversion rate in humans was, on average, 17%. CONCLUSION Our findings suggest that endogenous 16:1 t9 is not, as has been assumed, exclusively diet derived but may also be produced by the partial β oxidation of dietary 18:1 t11.

Evaluation of suppressive and pro-resolving effects of EPA and DHA in human primary monocytes and T-helper cells.

Despite their beneficial anti-inflammatory properties, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may increase the infection risk at high doses, likely by generating an immune-depressed state. To assess the contribution of different immune cell populations to the immunomodulatory fatty acid effect, we comparatively investigated several aspects of inflammation in human T-helper (Th) cells and monocytes. Both fatty acids, but DHA to a lesser extent compared with EPA, selectively and dose-dependently reduced the percentage of cytokine-expressing Th cells in a peroxisome proliferator-activated receptor (PPAR)γ-dependent fashion, whereas the expression of the cell surface marker CD69 was unaltered on activated T cells. In monocytes, both EPA and DHA increased interleukin (IL)-10 without affecting tumor necrosis factor (TNF)-α and IL-6. Cellular incorporation of EPA and DHA occurred mainly at the expense of arachidonic acid. Concomitantly, thromboxane B (TXB)2 and leukotriene B (LTB)4 in supernatants decreased, while levels of TXB3 and LTB5 increased. This increase was independent of activation and in accordance with cyclooxygenase expression patterns in monocytes. Moreover, EPA and DHA gave rise to a variety of mono- and trihydroxy derivatives of highly anti-inflammatory potential, such as resolvins and their precursors. Our results suggest that EPA and DHA do not generally affect immune cell functions in an inhibitory manner but rather promote pro-resolving responses.

Searching for health beneficial n‐3 and n‐6 fatty acids in plant seeds

Various plant seeds have received little attention in fatty acid research. Seeds from 30 species mainly of Boraginaceae and Primulaceae were analysed in order to identify potential new sources of the n-3 PUFA α-linolenic acid (ALA) and stearidonic acid (SDA) and of the n-6 PUFA γ-linolenic acid (GLA). The fatty acid distribution differed enormously between genera of the same family. Echium species (Boraginaceae) contained the highest amount of total n-3 PUFA (47.1%), predominantly ALA (36.6%) and SDA (10.5%) combined with high GLA (10.2%). Further species of Boraginaceae rich in both SDA and GLA were Omphalodes linifolia (8.4, 17.2%, resp.), Cerinthe minor (7.5, 9.9%, resp.) and Buglossoides purpureocaerulea (6.1, 16.6%, resp.). Alkanna species belonging to Boraginaceae had comparable amounts of ALA (37.3%) and GLA (11.4%) like Echium but lower SDA contents (3.7%). Different genera of Primulaceae (Dodecatheon and Primula) had varying ALA (14.8, 28.8%, resp.) and GLA portions (4.1, 1.5%, resp.), but similar amounts of SDA (4.9, 4.5%, resp.). Cannabis sativa cultivars (Cannabaceae) were rich in linoleic acid (57.1%), but poor in SDA and GLA (0.8, 2.7%, resp.). In conclusion, several of the presented plant seeds contain considerable amounts of n-3 PUFA and GLA, which could be relevant for nutritional purposes due to their biological function as precursors for eicosanoid synthesis. Practical applications N-3 PUFA are important for human health and nutrition. Unfortunately, due to the increasing world population, overfishing of the seas and generally low amounts of n-3 PUFA in major oil crops, there is a demand for new sources of n-3 PUFA. One approach involves searching for potential vegetable sources of n-3 PUFA; especially those rich in ALA and SDA. The conversion of ALA to SDA in humans is dependent on the rate-limiting Δ6-desaturation. Plant-derived SDA is therefore a promising precursor regarding the endogenous synthesis of n-3 long-chain PUFA in humans. The present study shows that, in addition to seed oil of Echium, other species of Boraginaceae (Cerinthe, Omphalodes, Lithospermum, Buglossoides) and Primulaceae (Dodecatheon, Primula), generally high in n-3 PUFA (30–50%), contain considerable amounts of SDA (5–10%). Therefore, these seed oils could be important for nutrition.

Trans-10,cis-12-CLA-Caused Lipodystrophy Is Associated with Profound Changes of Fatty Acid Profiles of Liver, White Adipose Tissue and Erythrocytes in Mice: Possible Link to Tissue-Specific Alterations of Fatty Acid Desaturation

Dietary supplementation with conjugated linoleic acid (CLA) has been shown to reduce body fat mass. To investigate the effects of individual CLA isomers on the fatty acid profiles of lipogenic (liver and white adipose) and lipid sensitive (erythrocyte) tissues, BALB/c mice were fed with 1 of 2 diets supplemented with either a c9,t11-CLA-enriched and t10,c12-CLA-free or a CLA-mixture containing both isomers in equal amounts (1% w/w of the diet) for 5 weeks. A control group was fed with a diet enriched in sunflower oil to energy balance the CLA. Compared to the t10,c12-CLA-free and the control diets, we observed a significant reduction of adipose tissue accompanied by fatty livers in the CLA-mix-fed group. These alterations in body fat distribution entailed a conspicuous shift of the fatty acid profiles of adipose tissue and livers. Liver enlargement was mainly caused by accumulation of C18 monoenes that accounted for 67 ± 1% of total fatty acid methyl esters. The significant reduction of the 18:0/18:1 desaturation index in the liver upon CLA-mix diet indicated high stearoyl-CoA desaturase activity. In contrast, reduction in white adipose tissue was largely driven by percental reduction of monounsaturated fatty acids (p ≤ 0.001). 16:0/ 16:1 and 18:0/18:1 desaturation indices for white adipose tissue significantly increased, suggesting an inhibition of stearoyl-CoA desaturase upon CLA-mix diet. The fatty acid profile of the erythrocytes widely reflected that of livers, depending on the supplemented diet. These profound changes in fatty acid composition of lipogenic organs due to t10,c12-CLA intake may be the consequence of function- al alterations of lipid metabolism.

Vaccenic acid-mediated reduction in cytokine production is independent of c9,t11-CLA in human peripheral blood mononuclear cells.

The ruminant trans fatty acid vaccenic acid (tVA) favorably alters markers of inflammation. However, it is not yet clear whether these effects are attributed to its endogenous partial conversion to c9,t11-CLA, which is known to possess anti-inflammatory properties. We compared the cytokine reducing potential of tVA to c9,t11-CLA in human T-helper (Th) cells as a main source of cytokine production during inflammation. Secondly, we assessed whether a bioconversion of tVA to c9,t11-CLA via stearoyl-CoA desaturase (SCD) encoded activity takes place in peripheral blood mononuclear cells (PBMC) in order to relate the outcomes of intracellular cytokine measurement to the degree of conversion. TVA reduced the percentage of both IL-2 and TNF-α expressing Th cells significantly, but to a lesser extent compared to c9,t11-CLA, as determined by flow cytometry after alloreactive stimulation of PBMC. Pre-treatment with the selective PPARγ antagonist T0070907 largely re-established the IL-2 and TNF-α positive Th cell population in both tVA and c9,t11-CLA treated cultures. Interestingly, while the portion of tVA dose-dependently increased within the cellular lipid fraction, the initially marginal amount of c9,t11-CLA remained unaltered. However, SCD mRNA although abundantly expressed in PBMC was not regulated by tVA. Conclusively, these results suggest that the cytokine reducing effect of tVA in human T cells is independent of c9,t11-CLA, since no bioconversion occurred. Moreover, the data provide evidence that tVA mechanistically acts in a manner similar to c9,t11-CLA.

Pentadecanoic and Heptadecanoic Acids: Multifaceted Odd-Chain Fatty Acids

The odd-chain fatty acids (OCFAs) pentadecanoic acid (15:0) and heptadecanoic acid (17:0), which account for only a small proportion of total saturated fatty acids in milk fat and ruminant meat, are accepted biomarkers of dairy fat intake. However, they can also be synthesized endogenously, for example, from gut-derived propionic acid (3:0). A number of studies have shown an inverse association between OCFA concentrations in human plasma phospholipids or RBCs and risk of type 2 diabetes and cardiovascular disease. We propose a possible involvement in metabolic regulation from the assumption that there is a link between 15:0 and 17:0 and the metabolism of other short-chain, medium-chain, and longer-chain OCFAs. The OCFAs 15:0 and 17:0 can be elongated to very-long-chain FAs (VLCFAs) such as tricosanoic acid (23:0) and pentacosanoic acid (25:0) in glycosphingolipids, particularly found in brain tissue, or can be derived from these VLCFAs. Their chains can be shortened, yielding propionyl-coenzyme A (CoA). Propionyl-CoA, by succinyl-CoA, can replenish the citric acid cycle (CAC) with anaplerotic intermediates and, thus, improve mitochondrial energy metabolism. Mitochondrial function is compromised in a number of disorders and may be impaired with increasing age. Optimizing anaplerotic intermediate availability for the CAC may help to cope with demands in times of increased metabolic stress and with aging. OCFAs may serve as substrates for synthesis of both odd-numbered VLCFAs and propionyl-CoA or store away excess propionic acid.

Abdominal symptoms in cystic fibrosis and their relation to genotype, history, clinical and laboratory findings

Background & aims Abdominal symptoms (AS) are a hallmark of the multiorgan-disease cystic fibrosis (CF). However, the abdominal involvement in CF is insufficiently understood and, compared to the pulmonary manifestation, still receives little scientific attention. Aims were to assess and quantify AS and to relate them to laboratory parameters, clinical findings, and medical history. Methods A total of 131 patients with CF of all ages were assessed with a new CF-specific questionnaire (JenAbdomen-CF score 1.0) on abdominal pain and non-pain symptoms, disorders of appetite, eating, and bowel movements as well as symptom-related quality of life. Results were metrically dimensioned and related to abdominal manifestations, history of surgery, P. aeruginosa and S. aureus colonization, genotype, liver enzymes, antibiotic therapy, lung function, and nutritional status. Results AS during the preceding 3 months were reported by all of our patients. Most common were lack of appetite (130/131) and loss of taste (119/131) followed by abdominal pain (104/131), flatulence (102/131), and distention (83/131). Significantly increased AS were found in patients with history of rectal prolapse (p = 0.013), distal intestinal obstruction syndrome (p = 0.013), laparotomy (p = 0.022), meconium ileus (p = 0.037), pancreas insufficiency (p = 0.042), or small bowel resection (p = 0.048) as well as in patients who have been intermittently colonized with P. aeruginosa (p = 0.006) compared to patients without history of these events. In contrast, no statistically significant associations were found to CF-associated liver disease, chronic pathogen colonization, lung function, CF-related diabetes, and nutritional status. Conclusion As the complex abdominal involvement in CF is still not fully understood, the assessment of the common AS is of major interest. In this regard, symptom questionnaires like the herein presented are meaningful and practical tools facilitating a wider understanding of the abdominal symptoms in CF. Furthermore, they render to evaluate possible abdominal effects of novel modulators of the underlying cystic fibrosis transmembrane (conductance) regulator (CFTR) defect.

Loss of FADS2 function severely impairs the use of HeLa cells as an in vitro model for host response studies involving fatty acid effects.

Scope Established epithelial cell lines equipped with pattern recognition receptors such as the Toll-like receptor (TLR)-2 are common tools for immune response studies on invading pathogens, e.g. the obligate intracellular species of Chlamydia. Moreover, such models are widely used to elucidate fatty acid-mediated immune effects. In several transformed cell lines, however, unusual loss of metabolic functions was described. The cell lines A549 and HeLa are poorly characterized in this respect. Therefore, we comparatively assessed the metabolic capacity of A549 and HeLa prior to proposed application as in vitro model for fatty acid effects on chlamydial infection. Methodology/Principal Findings We incubated both cell lines either with substrates (C18∶2n−6 or C18∶3n−3) or products (C18∶3n−6, C18∶4n−3) of fatty acid desaturase-2 (FADS2), and analysed the fatty acid profiles after 24 h and 72 h by gas chromatography. Based on these data, we suspected that the complete discontinuation of normal biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFA) in HeLa was due to loss of FADS2 function. Consequently, prostaglandin E2 (PGE2) formation was less inducible by TLR2 stimulation in HeLa, likely as a result of not only insufficient supply of precursors but also weak cyclooxygenase-2 (COX-2) response. In accordance, Chlamydia infection rates were consistently lower in HeLa than in A549. Sequence analysis revealed no alteration within the FADS2 gene in HeLa. The FADS2 expression level, however, was significantly lower and, in contrast to A549, not regulated by C18∶2n−6. A549 exhibited regular fatty acid metabolism and enzyme functionality. Conclusions/Significance Our data show that HeLa cells considerably differ from A549 at several stages of fatty acid metabolism. The poor metabolic potential of HeLa, mainly concerning FADS2 upstream of COX-2 function, calls into question whether these cells represent a good model to unveil fatty acid or downstream eicosanoid effects in the course of intracellular bacterial infection.

Dietary essential α-linolenic acid and linoleic acid differentially modulate TNFα-induced NFκB activity in FADS2-deficient HEK-293 cells

Abstract The pro- or anti-inflammatory bioactivity of dietary essential linoleic acid (LA) and alpha-linolenic acid (ALA) is mainly attributed to rate-limiting delta-6 desaturase (D6D) activity. The aim of this study was to analyze mechanisms of D6D-substrates ALA, LA and D6D-product gamma-linolenic acid (GLA) under D6D-deficient conditions. Fatty acid profiles (GC-MS), D6D gene expression (real-time RT-PCR) and NFκB activity (luciferase assay) were assessed in HEK293 cells. FADS2 gene expression was approved being marginal. Incubation with ALA or LA did not increase D6D products but their elongase products C20:3n-3 and C20:2n-6. Bypassing the D6D, GLA elevated C20:3n-6 and C20:4n-6. LA significantly increased (+18% at 60 μM; p < .001), ALA reduced (−32% at 100 μM; p < .001) and GLA did not specifically change NFκB activity. Our data indicate that D6D might not be essential for the distinct effects of LA and ALA on NFκB activity.