Ratio Of C18 Research Articles

Identification of genomic regions associated with fatty acid metabolism across blood, liver, backfat and muscle in pigs

BackgroundThe composition and distribution of fatty acids (FA) are important factors determining the quality, flavor, and nutrient value of meat. In addition, FAs synthesized in the body participate in energy metabolism and are involved in different regulatory pathways in the form of signaling molecules or by acting as agonist or antagonist ligands of different nuclear receptors. Finally, synthesis and catabolism of FAs affect adaptive immunity by regulating lymphocyte metabolism. The present study performed genome-wide association studies using FA profiles of blood, liver, backfat and muscle from 432 commercial Duroc pigs.ResultsTwenty-five genomic regions located on 15 Sus scrofa chromosomes (SSC) were detected. Annotation of the quantitative trait locus (QTL) regions identified 49 lipid metabolism-related candidate genes. Among these QTLs, four were identified in more than one tissue. The ratio of C20:4n-6/C20:3n-6 was associated with the region on SSC2 at 7.56–14.26 Mb for backfat, liver, and muscle. Members of the fatty acid desaturase gene cluster (FADS1, FADS2, and FADS3) are the most promising candidate genes in this region. Two QTL regions on SSC14 (103.81–115.64 Mb and 100.91–128.14 Mb) were identified for FA desaturation in backfat and muscle. In addition, two separate regions on SSC9 at 0 – 14.55 Mb and on SSC12 at 0–1.91 Mb were both associated with the same multiple FA traits for backfat, with candidate genes involved in de novo FA synthesis and triacylglycerol (TAG) metabolism, such as DGAT2 and FASN. The ratio C20:0/C18:0 was associated with the region on SSC5 at 64.84–78.32 Mb for backfat. Furthermore, the association of the C16:0 content with the region at 118.92–123.95 Mb on SSC4 was blood specific. Finally, candidate genes involved in de novo lipogenesis regulate T cell differentiation and promote the generation of palmitoleate, an adipokine that alleviates inflammation.ConclusionsSeveral SNPs and candidate genes were associated with lipid metabolism in blood, liver, backfat, and muscle. These results contribute to elucidating the molecular mechanisms implicated in the determination of the FA profile in different pig tissues and can be useful in selection programs that aim to improve health and energy metabolism in pigs.

Differences in individual bowhead whale Balaena mysticetus habitat use, foraging dive depth and diet during the peak feeding season

Shifts in zooplankton quantity and quality caused by climate change could challenge the ability of bowhead whales to meet their energetic requirements. When facing such selection pressure, intra-population variation dampens the negative effects and provides population-level resilience. Previous studies observed inter-individual diet variation in bowhead whales, but the mechanism responsible for the variation was undetermined. We investigated foraging variability in Eastern Canada-West Greenland bowhead whales using dietary biomarkers (stable isotopes, fatty acids) and movement data (satellite telemetry with time-depth recorders) from the same individuals. We found that bowhead whale individuals using distinct summer and fall foraging habitats displayed differences in horizontal movements, foraging dive depth, and diet. For individuals using the Canadian Arctic Archipelago habitat (Foxe Basin, Gulf of Boothia, Prince Regent Inlet, Lancaster Sound and Admiralty Inlet, Nunavut), they performed long distance movements across regions, and their foraging dive depth was generally shallow, but increased from July to November. These whales displayed higher δ13C and δ15N values and ratios of C16:1n7/C16:0. Individuals using the West Baffin Bay habitat (Cumberland Sound, Baffin Bay, Davis Strait) were more localized in their horizontal movements and consistent over time in their foraging dive depth, which was generally deeper. These whales displayed lower δ13C and δ15N values and ratios of C16:1n7/C16:0. Overall, this inter-individual variation in diet and foraging behaviour could indicate some niche variation which would be beneficial for the population under changing habitats and prey availability.

Serum Metabolomic Signatures for Knee Cartilage Volume Loss over 10 Years in Community-Dwelling Older Adults.

Osteoarthritis (OA) is the most prevalent joint disorder characterized by joint structural pathological changes with the loss of articular cartilage as its hallmark. Tools that can predict cartilage loss would help identify people at high risk, thus preventing OA development. The recent advance of the metabolomics provides a new avenue to systematically investigate metabolic alterations in disease and identify biomarkers for early diagnosis. Using a metabolomics approach, the current study aimed to identify serum metabolomic signatures for predicting knee cartilage volume loss over 10 years in the Tasmania Older Adult Cohort (TASOAC). Cartilage volume was measured in the medial, lateral, and patellar compartments of the knee by MRI at baseline and follow-up. Changes in cartilage volume over 10 years were calculated as percentage change per year. Fasting serum samples collected at 2.6-year follow-up were metabolomically profiled using the TMIC Prime Metabolomics Profiling Assay and pairwise metabolite ratios as the proxies of enzymatic reaction were calculated. Linear regression was used to identify metabolite ratio(s) associated with change in cartilage volume in each of the knee compartments with adjustment for age, sex, and BMI. The significance level was defined at α = 3.0 × 10−6 to control multiple testing. A total of 344 participants (51% females) were included in the study. The mean age was 62.83 ± 6.13 years and the mean BMI was 27.48 ± 4.41 kg/m2 at baseline. The average follow-up time was 10.84 ± 0.66 years. Cartilage volume was reduced by 1.34 ± 0.72%, 1.06 ± 0.58%, and 0.98 ± 0.46% per year in the medial, lateral, and patellar compartments, respectively. Our data showed that the increased ratios of hexadecenoylcarnitine (C16:1) to tetradecanoylcarnitine (C14) and C16:1 to dodecanoylcarnitine (C12) were associated with 0.12 ± 0.02% reduction per year in patellar cartilage volume (both p < 3.03 × 10−6). In conclusion, our data suggested that alteration of long chain fatty acid β-oxidation was involved in patellar cartilage loss. While confirmation is needed, the ratios of C16:1 to C14 and C12 might be used to predict long-term cartilage loss.

Effect of dietary fats on endogenous oleic acid biosynthesis in rat liver

Aim: Determine the effect of dietary fats with different fatty acid composition on the biosynthesis of oleic acid and its metabolic precursors in the liver .&#x0D; Methods: High linoleic sunflower oil (HLSO), high oleic sunflower oil (HOSO) and palm oil (PO) were used. Rats were fed a semi-synthetic fat-free diet (FFD) and fat diets containing 5 % of the above oils (instead of starch) for 30 days. Liver lipids were divided into 3 fractions: neutral lipids (NL), phospholipids (PL) and free fatty acids (FFA). The fatty acid composition of the fractions was determined by gas chromatography. The “activity” of fatty acid synthase was determined from the total content of the products of this reaction (C16:0 and C16:1). The “activity” of palmitic acid elongase was determined by the ratio С18:0/С16:0, as well as by the formula (С18:0+С18:1)/(С16:0–С16:1). The “activity” of stearic acid desaturase (SCD1) was determined by the ratio C16:1/C16:0 (SCD16) and by the ratio C18:1/C18:0 (SCD18).&#x0D; Results: In rats treated with fat diets, the content of palmitic and oleic acids is reduced only in the NL fraction, and to the greatest extent when consuming the diet with HLSO. The “activity” of palmitic acid elongase increases significantly with the consumption of a diet with HLSO. SCD16 desaturase “activity” decreases with fat diet, while SCD18 desaturase “activity” increases. The level of SCD18 is significantly higher than the level of SCD16. Consumption of HLSO reduces the content of ω-3 PUFA in rat liver lipids, while the intake of HOSO increases it.&#x0D; Conclusions: HLSO diet reduces the endogenous biosynthesis of oleic and palmitic acids, as determined by the analysis of the rat liver NL fraction. A fat diet reduces SCD16 “activity” but increases SCD18 “activity”, especially when fed a diet with HOSO. The diet with HLSO reduces the content of ω-3 PUFA in liver lipids.

Chemotaxonomic and evolutionary perspectives of Bryophyta based on multivariate analysis of fatty acid fingerprints of Eastern Himalayan mosses.

Bryophyta comprises one of the earliest lineages of land plants that had implemented remarkable innovations to their lipid metabolic systems for successful adaptation to terrestrial habitat. This study presents a comprehensive investigation of fatty acid profiles of mosses from Eastern Himalayas with an aim to trace their chemotaxonomic and evolutionary implications. Fatty acid compositions of 40 random mosses belonging to major families of Bryophyta were explored by gas chromatographic analysis. A diverse array of saturated, monounsaturated and polyunsaturated fatty acids including rare acetylenic fatty acids were detected. Hexadecanoic acid (C16:0), 9,12 (Z,Z)-octadecadienoic acid (C18:2n6) and 9,12,15 (Z,Z,Z)-octadecatrienoic acid (C18:3n3) were the predominant fatty acids in all the mosses. However, quantitative variation of C20 polyunsaturated fatty acids (PUFAs), specifically 5,8,11,14 (Z,Z,Z,Z)-eicosatetraenoic acid (C20:4n6), among the investigated mosses was the most prominent outcome. The diplolepidous members of Bryidae, especially the mosses of Hypnales, Bryales and Bartramiales contained higher amount of C20 PUFAs compared with the haplolepidous orders. Principal component analyses based on individual fatty acids and other related parameters validated C20:4n6 content and the ratio of C20:4n6/C18:2n6 as the apparent chemotaxonomic discriminants. The prevalent notion of considering 9,12,15-octadecatrien-6-ynoic acid (C18:4a) as the chemomarker of Dicranaceae has also been challenged, since the compound was detected not only in different families of Dicranales, but also in a Pottiales member, Leptodontium viticulosoides. Therefore, an ensemble of fatty acids instead of a single one can be considered as the chemical signature for taxonomic interpretation which may also be vital from an evolutionary standpoint.

Comparative Study of Volatile Compounds and Sensory Characteristics of Dalmatian Monovarietal Virgin Olive Oils.

Volatile compounds are chemical species responsible for the distinctive aroma of virgin olive oil. Monovarietal olive oils have a peculiar composition of volatiles, some of which are varietal descriptors. In this paper, the total phenolic content (TPC), fatty acid composition, volatile compounds, and sensory profile of monovarietal olive oils from four Dalmatian most common olive cultivars—Oblica, Lastovka, Levantinka, and Krvavica—were studied. The volatile composition of olive oils was analyzed using headspace solid-phase microextraction with gas chromatography/mass spectrometry. The highest mean TPC value was measured in Oblica and Krvavica oils (around 438 mg/kg). The difference among cultivars for fatty acids composition was detected for C16:1, C17:0, C18:1, C18:2, and the ratio C18:1/C18:2. Krvavica oils showed clear differences in fatty acid composition compared to oils from other cultivars. The most prevalent volatile compound in all oils was C6 aldehyde E-2-hexenal, with the highest value detected in Levantinka oils (75.89%), followed by Lastovka (55.27%) and Oblica (54.86%). Oblica oils had the highest value of Z-3-hexen-1-ol, which influenced its characteristic banana fruitiness, detected only in this oil. Lastovka oils had the highest amount of several volatiles (heptanal, Z-2-heptenal, hexanal, hexyl acetate), with a unique woody sensation and the highest astringency among all studied cultivars. Levantinka oils had the highest level of almond fruitiness, while Krvavica oils had the highest level of grass fruitiness.

Spatial heterogeneity in fatty acid abundance and composition across surface sediments of Lake Taihu, Eastern China: Implications for the use of lipids in evaluating carbon cycling and burial in lake systems

Fatty acids (FAs) present in the surface sediments of Lake Taihu were analyzed for spatial heterogeneity in abundance and composition in order to test the suitability of these lipids to indicate variation in sources and preservation status of organic matter (OM) in sediments. The results indicate that terrestrial plant-derived FAs were relatively enriched in Meiliang and Zhushan Bays, the most eutrophic regions of Lake Taihu, while FAs of phytoplankton origin were relatively low. This unexpected result might reflect a preferential degradation of phytoplankton OM and phytoplankton-derived FAs. Furthermore, massive inputs of refractory terrestrial OM could significantly dilute concentrations of phytoplankton FAs. In sediments from East Bay, phytoplankton-derived FAs were more abundant than in Zhushan Bay, although this region had the lowest levels of nutrients and the lowest phytoplankton productivity. This result was attributed to a greatly enhanced preservation of labile FAs, probably caused by reduced sediment resuspension in this region with dense growth of submerged macrophytes. Phytoplankton productivity and terrestrial OM inputs were moderate in Central Region, but abundances of all FAs and ratios of C16:1/n-C16, C18:1/n-C18 and C18:1ω7/C18:1ω9 both reached their lowest in sediments from this region, possibly as a result of significant degradation of FAs driven by strong sediment resuspension. Sediments from Gonghu Bay and Southern Region were relatively enriched in phytoplankton FAs, and this was ascribed to low inputs of terrestrial OM, which limited the dilution effect. In contrast to FAs, short-chain n-alkane abundances provided an accurate indication of variation in phytoplankton input.

The effect of dietary pumpkin seed cake and extruded linseed on blood haemato-chemicals and milk quality in Alpine goats during early lactation

Due to the high content of crude protein and high concentration of unsaturated fatty acids, pumpkin seed cake (PSC) could be a good quality feedstuff for ruminants, while extruded linseed (ELS) has already shown some beneficial effect on fatty acids proportion of goat milk. Besides, lactation is the most demanding period when monitoring the metabolic condition of animal. Therefore, the aim of this study was to determine the effect of PSC and ELS replacing soybean meal in diets of dairy goats on blood haemato-chemical parameters and milk quality. A 28 lactating French Alpine dairy goats were monitored within 20 days in early lactation. Diet of each groups had a balanced content of energy and crude protein, and a slight difference in lipid content. Goats in control group (n = 9) received soybean meal and extruded soybean. In experimental groups soybean was partially replaced with ELS (n = 10) or completely with PSC (n = 9). Dietary treatments had no effect on haemato-chemical parameters, although PSC increased concentration of globulins in serum. PSC lowered linoleic acid compared to control. ELS increased proportion of α-linolenic acid, eicosapentaenoic acid, and total n-3 fatty acids in milk. Positive correlations were found between non-esterified fatty acids (NEFA) and ratio C18:1/C15:0, NEFA and ratio C17:0/C15:0, as well as β-hydroxybutyrate and ratio C17:0/C15:0. The replacement of soybean meal with PSC or partially with ELS is feasible with respect to haemato-chemical parameters of early lactating dairy goats, while ELS had much beneficial effect on fatty acids compared to PSC.

The C18:3n6/C22:4n6 ratio is a good lipid marker of chronic kidney disease (CKD) progression

BackgroundChronic kidney disease (CKD) is a major challenge for public health due to increased risk of cardiovascular diseases (CVD) and premature death. The aim of this study was to determine the clinical picture of FA and the course of the pathophysiological mechanisms of CKD.MethodsThe study involved 149 patients with CKD and a control group including 43 people. Fatty acid profiles were investigated using gas chromatography. A total of 30 fatty acids and their derivatives were identified and quantified. The omega3, omega6, SFA, MUFA, and PUFA fatty acid contents were calculated. The correlation matrix was obtained for parameters relating to patients with CKD vs. FA, taking patients’ sex into consideration. The index C18:3n6/C22:4n6 was calculated according to the length of the treatment. Statistica 12.0 software (Tulsa, Oklahoma, USA) was used for the statistical analyses.ResultsThe results showed decreased levels of total PUFA and increased concentrations of MUFA, including the activation of the palmitic and oleic acid pathway. An increase in the levels of n-6 9C22: 4n6 family fatty acids in all the patients and a reduction in the n-3 family (EPA, DHA) were observed. C18:3n6 was negatively correlated and C22:4n6 was positively correlated with the duration of the treatment. The index C18:3n6/C22:4n6 was defined as a new marker in the progression of the disease. Moreover, the index C18:3n6/ C22:4n6 was drastically decreased in later period. Nervonic acid was higher in the CKD group. In the group of men with CKD, there was a negative correlation between the excretion of K+, anthropometric measurements, and the levels of EPA and DHA.ConclusionsThe course of inflammation in CKD occurs through the decrease in PUFA and the synthesis of MUFA. The dominating cascade of changes is the elongation of GLA-C18:3n6 into DGLA-C20:3n6 and AA-C20:4n6. As CKD progresses, along with worsening anthropometrical parameters and increased secretion of potassium, the activity of Ʌ6-desaturase decreases, reducing the synthesis of EPA and DHA. The synthesis of AdA-C22:4n6 increases and the ratio C18:3n6/C22:4n6 drastically decreases after 5 years. This parameter can be used to diagnose disease progression.

Fatty acid-driven modifications in T-cell profiles in non-alcoholic fatty liver disease patients.

The interaction between T-cells/fatty acids involved in non-alcoholic fatty liver disease (NAFLD) and liver fibrosis progression is poorly understood. In this study, we conducted a comprehensive analysis of T-cell profiles of NAFLD patients to better understand their relationship with fatty acids and relevance to liver fibrosis. We analyzed the differences in T-cell profiles of peripheral blood mononuclear cells (PBMCs) between 40 NAFLD patients and 5 healthy volunteers (HVs), and their relationship with liver fibrosis stage or progression. Moreover, we analyzed the relationship between T-cell profiles and fatty acid compositions in vivo, and changes in T-cell profiles after treatment with fatty acids in vitro. T-cell profiles of NAFLD patients were different from those of HVs. The CD25+CD45+CD4+ T-cell frequency was increased in NAFLD patients with high liver fibrosis stage and progression, and this indicated immune activation. Despite such a state of immune activation, the PD1+CD4+ T-cell frequency was decreased in the same patients group. The PD1+CD4+ T-cell frequency had a significantly negative correlation with the serum fatty acid composition ratio C16:1n7/C16:0. Moreover, the PD1+CD4+ T-cell frequency was significantly decreased by in vitro treatment with fatty acids. In addition, its rate of frequency change was significantly different between C16:0 and C16:1n7 and decreased by artificially increasing the C16:1n7/C16:0 ratio. The analysis of PBMCs in NAFLD patients showed that T-cell profiles were different from those of HVs. And, it suggested that fatty acids modified T-cell profiles and were involved in liver fibrosis in NAFLD patients.

Short communication: dietary vitamin A restriction may improve meat quality parameters in fat-tailed lambs

Thirty fat-tailed Mehraban ram lambs were randomly allotted into three vitamin A (VA) dietary treatment groups: either 100 (VA100), 50 (VA50), or 25% (VA25) of the recommended daily vitamin A requirements. Treatment had no effect on feed intake, daily live weight gain, cold carcass weight, and dressing percentage. In M. longissimus lumborum (LL) of VA100 lambs, malondialdehyde level was greater, but ether-extractable intramuscular fat concentration was lower. The proportion of C16:0 and C20:0 fatty acids in total fatty acids of LL was lower in VA100 lambs, compared to VA50 and VA25 lambs. Conversely, greater proportions of C17:0, C17:1, C18:1, and C18:2 fatty acids were recorded in VA100 lambs. Stearoyl-CoA desaturase activity index (the ratios of C16:0 to C16:1 and C18:0 to C18:1) was not influenced by dietary vitamin A level. Future research is needed to determine the optimum level of dietary vitamin A concentration for deposition of greater intramuscular fat in fat-tailed sheep.

Linoleic acid metabolic pathway allows for an efficient increase of intramuscular fat content in pigs

BackgroundIntramuscular fat (IMF) content is a relevant trait for high-quality meat products such as dry-cured ham, but increasing IMF has the undesirable correlated effect of decreasing lean growth. Thus, there is a need to find selection criteria for IMF independent from lean growth. In pigs, the proportion of linoleic (C18:2) and arachidonic (C20:4) acids decline with fat deposition and therefore they can be considered as indicators of fatness. The aim of this research was to estimate the genetic variation for C18:2 and C20:4 in IMF and their genetic correlations with IMF and lean growth traits, with the objective to assess their potential as specific biomarkers of IMF. The analysis was conducted using a full-pedigreed Duroc resource line with 91,448 records of body weight and backfat thickness (BT) at 180 days of age and 1371 records of fatty acid composition in the muscle gluteus medius.ResultsThe heritability estimates for C18:2 and C20:4 in IMF, whether expressed in absolute (mg/g of muscle) or in relative (mg/g of fatty acid) terms, as well as for their ratio (C20:4/C18:2), were high (> 0.40), revealing that the C18:2 to C20:4 pathway is subjected to substantial genetic influence. Litter effects were not negligible, with values ranging from 8% to 15% of the phenotypic variance. The genetic correlations of C18:2 and C20:4 with IMF and BT were negative (− 0.75 to − 0.66, for IMF, and − 0.64 to − 0.36, for BT), if expressed in relative values, but almost null (− 0.04 to 0.07), if expressed in absolute values, except for C18:2 with IMF, which was highly positive (0.88). The ratio of C20:4 to C18:2 also displayed a stronger genetic correlation with IMF (− 0.59) than with BT (− 0.10).ConclusionsThe amount of C18:2 in muscle can be used as an IMF-specific biomarker. Selection for the absolute amount of C18:2 is expected to deliver a similar response outcome as selection for IMF at restrained BT. Further genetic analysis of the C18:2 metabolic pathway may provide new insights into differential fat deposition among adipose tissues and on candidate genes for molecular markers targeting specifically for one of them.

Changes of free fatty acid composition and number of lactic acid bacteria in three functional goat and sheep milk products fortified with inulin or fish oil

ABSTRACTInulin and fish oil rich in omega-3 fatty acid were applied to yoghurt, kefir, and smearcase made from goat and sheep milk, and their impact on fatty acid composition was investigated at 8°C throughout 40 days. The number of lactic acid bacteria (LAB) was significantly diminished within 16 days, and by the end of the storage period the population size was decreased by 3 orders of magnitude in fish oil fortified samples. In inulin-fortified samples, a significant decrease in LAB number (by 2.5–3 orders of magnitude) was observed just by the end of the storage time, while the amount of unsaturated free fatty acids was increased. The extent of lipolysis and the resulted amount of free fatty acids exhibited varying feature depending on the composition of the product. Goat and sheep milk products exhibit analogous trends in terms of change in fatty acid composition with one exception: the ratio of free C16:0 was increased by 10% for goat milk products, while for the sheep milk products only by 3%. Ratio of C16:0 did not change during storage of sheep yoghurt as a result of inulin fortification. In contrast, 13% increase of this parameter was observed in case of the product variant prepared with fish oil addition. It might be stated that fortification with prebiotics can be regarded as a better way to improve the biological value of dairy products than that with fish oil.

Dietary polyunsaturated fatty acids mediate the inverse association of stearoyl-CoA desaturase activity with the risk of fatty liver in dyslipidaemic individuals.

The activity of stearoyl-CoA desaturase-1 (SCD1) is increased in non-alcoholic fatty liver disease (NAFLD). Polyunsaturated fatty acids (PUFA) inhibit SCD1, but clinical studies on whether all dietary PUFA species are equal in SCD1 inhibition are scarce. Serum phospholipids are an objective proxy of dietary intake of plant-derived PUFA (C18:2n-6, C18:3n-3) and marine-derived PUFA (C20:5n-3, C22:6n-3). In 355 participants with primary dyslipidemia, we cross-sectionally investigated whether the presumed association between surrogate markers of NAFLD and SCD1 activity is mediated by intake of PUFA, and, if it is, what PUFA species are relevant in this regard. We determined the fatty acid profile of serum phospholipids by gas chromatography, and used the ratio C16:1n-7/C16:0 as a marker of SCD1 activity. NAFLD was diagnosed by values ≥ 60 in the fatty liver index (FLI), a surrogate recently validated against ultrasonography. FLI ≥ 60 was detected in 37.5% (n = 133) of study participants. In a multivariate model, SCD1 activity showed an expected significant association with the risk of NAFLD, with odds ratio (OR) (95% confidence interval) of 1.44 (1.04-2.01) for each 0.01 increase. In a model further allowing the stepwise inclusion of plant-derived PUFA, marine-derived PUFA, and total PUFA (vegetable + marine), total PUFA replaced SCD1 activity as a significant (inverse) association of NAFLD, with OR 0.89 (0.81-0.99). Total PUFA, regardless of their origin, mediates the relationship between SCD1 activity and NAFLD. This provides a new insight in the protective effects of PUFA against NAFLD, heretofore mostly focussed on PUFA species from marine origin.

The Potential of Alkyl Amides as Novel Biomarkers and Their Application to Paleocultural Deposits in China

A series of alkyl amides was detected and identified in the sedimentary record from an archaeological site at Yuchisi, Mengcheng, Anhui, China. The alkyl amides profiles change abruptly at the depth corresponding to the transition between two prehistoric cultures, which also corresponds to an abrupt change in the fatty acid ratio C18:2/C18:0. The different patterns of variation of the longer and shorter chain alkyl amides at the depth of the cultural transition may reflect differences in their response to external environmental changes, as well as different sources. This is the first study of the stratigraphic variation of alkyl amides in sediments, and their first application to assess paleoenvironmental changes. We suggest that alkyl amides may have potential as new biomarkers in archeological and paleoenvironmental studies.

22 - Vitamin E (RRR-α-tocopherol) decreases hepatic de novo lipogenesis

Non-alcoholic fatty liver disease (NAFLD) is becoming a major hepatic disease in the Western world. The hallmark feature of NAFLD is steatosis, the accumulation of hepatic triacylglycerol (TG), which results from the disruption of metabolic pathways, one of which is de novo lipogenesis (DNL). RRR-α-tocopherol (αT) can reduce steatosis in animals and NAFLD patients through a yet-unknown mechanism. We aimed to identify the mechanism by which αT decreases liver TG and whether its antioxidant (AO) effect is required for this effect. HepG2 cells cultivated under high glucose medium (25 mmol/L) had a 19% increase in lipid accumulation and 2-fold increase in expression of fatty acid synthase (FASN), a key enzyme in DNL, which were reversed by αT to control levels in a dose dependent manner (25-100 µmol/L, 48h). Similarly, 100 µmol/L of αT decreased incorporation of 14C glucose into lipids by 24%. We confirmed this effect in vivo in plasma samples from NAFLD patients (n=21), obtained before and after 4 weeks of αT supplementation (NCT01792115). Liver TG, measured by 1H-magnetic resonance spectroscopy, decreased in 55% of the patients. The lipogenic index, the ratio of C16:0/C18:2n6 in VLDL, reflects hepatic DNL. Patients with reduction in liver TG after 4 weeks of αT also had a significant reduction in the lipogenic index compared to non-responders (p=0.01). To address if αT reduces DNL through its AO function we synthesized methoxy-αT (m-αT), a lipid-soluble αT derivate lacking the AO function and compared it to αT, trolox (water-soluble αT analogue with AO capacity), and probucol (lipid-soluble AO). In our lipogenic HepG2 model, αT, m-αT, trolox and probucol decreased lipid content by max. 18, 0, 0 and 13%, respectively. Thus, our data indicates that αT reduces hepatic DNL in vitro and in vivo through a mechanism that is likely dependent on its antioxidative activity in the lipid compartment.

Chemometric characterization of virgin olive oils of the two major Cypriot cultivars based on their fatty acid composition

The effects of the geographical region and the botanical origin of olive oils on the profile of fatty acids isolated from monovarietal virgin olive oils from Cyprus were investigated, in order to establish, for the first time, promising models for authentication and classification of monovarietal virgin olive oils produced on the island. The two dominant Cypriot olive cultivars, Cypriot (ladoelia), and Koroneiki (lianolia), were analyzed for fatty acid composition by GC/FID after preparation of Fatty Acid Methyl Esters from olive oil, using a cold esterification method. The data obtained were analyzed statistically using multivariate and univariate ANOVA, principal components analysis (PCA) and hierarchical cluster analysis. Results showed that the olive oils can be separated into two distinct groups using the FAME data bank obtained from 225 samples. Significant differences in the proportion of some variables such as polyunsaturated linoleic acid, and the ratio C18:1/C18:2 from oils of different varieties and geographical regions were detected. The ratios C18:1/C18:2 and MUFA/PUFA, as well SFA, ω-9 and PUFA showed the higher discriminant power based on the cultivar.

Dysregulations in circulating sphingolipids associate with disease activity indices in female patients with systemic lupus erythematosus: a cross-sectional study

Objective The objective of this study was to investigate the association of clinical and renal disease activity with circulating sphingolipids in patients with systemic lupus erythematosus. Methods We used liquid chromatography tandem mass spectrometry to measure the levels of 27 sphingolipids in plasma from 107 female systemic lupus erythematosus patients and 23 controls selected using a design of experiment approach. We investigated the associations between sphingolipids and two disease activity indices, the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index. Damage was scored according to the Systemic Lupus International Collaborating Clinics damage index. Renal activity was evaluated with the British Island Lupus Activity Group index. The effects of immunosuppressive treatment on sphingolipid levels were evaluated before and after treatment in 22 female systemic lupus erythematosus patients with active disease. Results Circulating sphingolipids from the ceramide and hexosylceramide families were increased, and sphingoid bases were decreased, in systemic lupus erythematosus patients compared to controls. The ratio of C16:0-ceramide to sphingosine-1-phosphate was the best discriminator between patients and controls, with an area under the receiver-operating curve of 0.77. The C16:0-ceramide to sphingosine-1-phosphate ratio was associated with ongoing disease activity according to the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index, but not with accumulated damage according to the Systemic Lupus International Collaborating Clinics Damage Index. Levels of C16:0- and C24:1-hexosylceramides were able to discriminate patients with current versus inactive/no renal involvement. All dysregulated sphingolipids were normalized after immunosuppressive treatment. Conclusion We provide evidence that sphingolipids are dysregulated in systemic lupus erythematosus and associated with disease activity. This study demonstrates the utility of simultaneously targeting multiple components of a pathway to establish disease associations.

The effect of coffee intake on lysophosphatidylcholines: A targeted metabolomic approach

Lysophosphatidylcholines (lysoPC) are known to be a pathological component of oxidized-LDL, and several studies demonstrate its pro-inflammatory properties invitro. Nevertheless, bioactive compounds found in coffee, such as phenolic acids might inhibit LDL oxidation. The relationship between coffee consumption and lysoPC has not been described previously in humans. The aim of the present study was to assess the association between coffee intake and plasma lysoPC levels in adults. Data was from the "Health Survey of Sao Paulo (ISA-Capital)", a cross-sectional population-based survey in Sao Paulo, among 169 individuals aged 20 years or older. This population was categorized into three groups: non-coffee consumers (0mL/day-G1), low coffee consumers (≤100mL/day-G2), and high coffee consumers (>100mL/day-G3). Usual coffee intake was estimated by two 24HR and one FFQ, using Multiple Source Method. Quantification of the metabolites was performed by mass spectrometry (FIA-MS/MS and HPLC-MS/MS) and 14 lysoPC species were identified. The association between coffee intake and lysoPC was analyzed by multiple linear regression adjusted for age, sex, household per capita income, smoking, physical activity, body mass index, total energy intake, use of drugs, vegetables and fruit consumption and caffeine intake. LysoPC levels were significantly lower in G3 than in G1, for the lysoPC a C16:1 (β=-0.56; p=0.014), lysoPC a C18:1 (β=-2.57; p=0.018), and lysoPC a C20:4 (β=-1.14; p=0.037). In opposition, the ratios of C16:0/C16:1 and C18:0/18:1 was higher in G3 (β=5.04; p=0.025 and β=0.28; p=0.003, respectively). LysoPC profile differed according to coffee intake, showing a possible beneficial health effect of this beverage on inflammatory and oxidative processes.

The abrupt climate change near 4,400 yr BP on the cultural transition in Yuchisi, China and its global linkage.

Extreme climatic events have profound impacts on human society. Here we present the results of a study of organic biomarkers within a sedimentary section at the archaeological site of Yuchisi, eastern China, in order to reconstruct climatic variability during the Dawenkou (5,050–4,400 yr BP) and Longshan (4,400–4,000 yr BP) cultures. At ~4,400 yr BP, within the cultural transition horizon, abrupt changes in biomarkers, such as the fatty acid ratio C18:2/C18:0, 2C31/(C27 + C29), n-C18-ol and n-C30-ol, indicate the occurrence of local climate changes over the course of a few decades. These changes occurred during the transition from the Holocene warm period to a subsequent cold period which lasted for the following 600 years. This climatic shift has been recorded at numerous sites worldwide, and it is likely to have been the main cause of the widespread collapse of many isolated cultures at that time. The palaeoclimatic and archaeological data from the Yuchisi sediments may provide new insights into the relationship between climate change and prehistoric cultural transitions.