Rational engineering of complicated metabolic networks involved in the production of biologically active plant compounds has been greatly impeded by our poor understanding of the regulatory and ...metabolic pathways underlying the biosynthesis of these compounds. Whereas comprehensive genome-wide functional genomics approaches can be successfully applied to analyze a select number of model plants, these holistic approaches are not yet available for the study of nonmodel plants that include most, if not all, medicinal plants. We report here a comprehensive profiling analysis of the Madagascar periwinkle (Catharanthus roseus), a source of the anticancer drugs vinblastine and vincristine. Genomewide transcript profiling by cDNA-amplified fragment-length polymorphism combined with metabolic profiling of elicited C. roseus cell cultures yielded a collection of known and previously undescribed transcript tags and metabolites associated with terpenoid indole alkaloids. Previously undescribed gene-to-gene and geneto-metabolite networks were drawn up by searching for correlations between the expression profiles of 417 gene tags and the accumulation profiles of 178 metabolite peaks. These networks revealed that the different branches of terpenoid indole alkaloid biosynthesis and various other metabolic pathways are subject to differing hormonal regulation. These networks also served to identify a select number of genes and metabolites likely to be involved in the biosynthesis of terpenoid indole alkaloids. This study provides the basis for a better understanding of periwinkle secondary metabolism and increases the practical potential of metabolic engineering of this important medicinal plant.
Plant cell cultures from cloudberry, lingonberry and stoneberry were studied in terms of their nutritional properties as food. Carbohydrate, lipid and protein composition, in vitro protein ...digestibility and sensory properties were investigated. Dietary fibre content varied between 21.2 and 36.7%, starch content between 0.3 and 1.3% and free sugar content between 17.6 and 33.6%. Glucose and fructose were the most abundant sugars. High protein contents between 13.7 and 18.9% were recorded and all samples had a balanced amino acid profile. In vitro protein digestion assay showed hydrolysis by digestive enzymes in fresh cells but only limited hydrolysis in freeze-dried samples. The lipid analysis indicated that the berry cells were rich sources of essential, polyunsaturated fatty acids. In sensory evaluation, all fresh berry cells showed fresh odour and flavour. Fresh cell cultures displayed a rather sandy, coarse mouthfeel, whereas freeze-dried cells melted quickly in the mouth. All in all the potential of plant cells as food was confirmed.
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•Plant cells exhibit nutritional qualities suitable for food applications.•High DF and protein content compared to berry fruits.•Accumulation of essential, polyunsaturated fatty acids•Adequate sensory quality with some berry-like odours
Lipids are an important and highly diverse class of molecules having structural, energy storage and signaling roles. Modern analytical technologies afford screening of many lipid molecular species in ...parallel. One of the biggest challenges of lipidomics is elucidation of important pathobiological phenomena from the integration of the large amounts of new data becoming available.
We present computational and informatics approaches to study lipid molecular profiles in the context of known metabolic pathways and established pathophysiological responses, utilizing information obtained from modern analytical technologies. In order to facilitate identification of lipids, we compute the scaffold of theoretically possible lipids based on known lipid building blocks such as polar head groups and fatty acids. Each compound entry is linked to the available information on lipid pathways and contains the information that can be utilized for its automated identification from high-throughput UPLC/MS-based lipidomics experiments. The utility of our approach is demonstrated by its application to the lipidomic characterization of the fatty liver of the genetically obese insulin resistant ob/ob mouse model. We investigate the changes of correlation structure of the lipidome using multivariate analysis, as well as reconstruct the pathways for specific molecular species of interest using available lipidomic and gene expression data.
The methodology presented herein facilitates identification and interpretation of high-throughput lipidomics data. In the context of the ob/ob mouse liver profiling, we have identified the parallel associations between the elevated triacylglycerol levels and the ceramides, as well as the putative activated ceramide-synthesis pathways.
We have explored human aqueous tear fluid lipidome with an emphasis to identify the major lipids. We also address the physiological significance of the lipidome. The tears were analysed using thin ...layer chromatographic, enzymatic and mass spectrometric techniques. To emphasize the physiological aspect of the lipidome, we modelled the spreading of the non-polar tear fluid lipids at air-water interface in macroscopic scale with olive oil and egg yolk phosphatidylcholine. Based on enzymatic analysis the respective concentrations of choline-containing lipids, triglycerides, and cholesteryl esters were 48±14, 10±0, and 21±18 µM. Ultra performance liquid chromatography quadrupole time of flight mass spectrometry analysis showed that phosphatidylcholine and phosphatidylethanolamine were the two most common polar lipids comprising 88±6% of all identified lipids. Triglycerides were the only non-polar lipids detected in mass spectrometric analysis i.e. no cholesteryl or wax esters were identified. The spreading experiments show that the presence of polar lipids is an absolute necessity for a proper spreading of non-polar tear fluid lipids. We provide evidence that polar lipids are the most common lipid species. Furthermore, we provide a physiological rationale for the observed lipid composition. The results open insights into the functional role of lipids in the tear fluid and also aids in providing new means to understand and treat diseases of the ocular surface.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Children developing type 1 diabetes may have risk markers already in their umbilical cord blood. It is hypothesized that the risk for type 1 diabetes at an early age may be increased by a pathogenic ...pregnancy and be reflected in altered cord-blood composition. This study used metabolomics to test if the cord-blood lipidome was affected in children diagnosed with type 1 diabetes before 8 years of age. The present case-control study of 76 index children diagnosed with type 1 diabetes before 8 years of age and 76 healthy control subjects matched for HLA risk, sex, and date of birth, as well as the mother's age and gestational age, revealed that cord-blood phosphatidylcholines and phosphatidylethanolamines were significantly decreased in children diagnosed with type 1 diabetes before 4 years of age. Reduced levels of triglycerides correlated to gestational age in index and control children and to age at diagnosis only in the index children. Finally, gestational infection during the first trimester was associated with lower cord-blood total lysophosphatidylcholines in index and control children. In conclusion, metabolomics of umbilical cord blood may identify children at increased risk for type 1 diabetes. Low phospholipid levels at birth may represent key mediators of the immune system and contribute to early induction of islet autoimmunity.
Cell cultures originating from 12 different plant species growing or grown in the Nordic countries were screened for their ability to synthesize polyphenols to assess their suitability for future ...studies and applications. The focus was on plant families Rosaceae and Ericaceae. On average, the Rosaceae cultures were the most efficient to produce hydrolysable tannins and the Ericaceae cultures were the most efficient to produce proanthocyanidins. This is in line with the general trend of polyphenols found in Rosaceae and Ericaceae leaves and fruits, even though several individual cell cultures differed from natural plants in their polyphenolic composition. Overall, several of the studied cell cultures exhibited capability in producing a large variety of polyphenols, including tannins with a high molecular weight, thus also showing promise for further studies concerning, for example, the accumulation of specific polyphenols or biosynthesis of polyphenols in the cell cultures.
In this paper, analytical methodologies for the global profiling of lipids in serum and tissue samples are reported. The sample preparation is based on a modified Folch extraction, and the analysis ...is carried out with ultrahigh-performance liquid chromatography combined with mass spectrometry (UPLC-MS). For further identification, MSn mass spectrometry is carried out utilizing an LTQ-Orbitrap mass spectrometry as the detector. Such a system affords determination of accurate masses and is thus a highly useful tool for lipid identification. The repeatability of the analysis proved to be good, with relative standard errors for spiked samples being between 4.51 and 10.44%. The throughput of the methodology described here is over 100 samples a day.
Persons with schizophrenia and other psychotic disorders have a high prevalence of obesity, impaired glucose tolerance, and lipid abnormalities, particularly hypertriglyceridemia and low high-density ...lipoprotein. More detailed molecular information on the metabolic abnormalities may reveal clues about the pathophysiology of these changes, as well as about disease specificity.
We applied comprehensive metabolomics in serum samples from a general population-based study in Finland. The study included all persons with DSM-IV primary psychotic disorder (schizophrenia, n = 45; other non-affective psychosis (ONAP), n = 57; affective psychosis, n = 37) and controls matched by age, sex, and region of residence. Two analytical platforms for metabolomics were applied to all serum samples: a global lipidomics platform based on ultra-performance liquid chromatography coupled to mass spectrometry, which covers molecular lipids such as phospholipids and neutral lipids; and a platform for small polar metabolites based on two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC × GC-TOFMS).
Compared with their matched controls, persons with schizophrenia had significantly higher metabolite levels in six lipid clusters containing mainly saturated triglycerides, and in two small-molecule clusters containing, among other metabolites, (1) branched chain amino acids, phenylalanine and tyrosine, and (2) proline, glutamic, lactic and pyruvic acids. Among these, serum glutamic acid was elevated in all psychoses (P = 0.0020) compared to controls, while proline upregulation (P = 0.000023) was specific to schizophrenia. After adjusting for medication and metabolic comorbidity in linear mixed models, schizophrenia remained independently associated with higher levels in seven of these eight clusters (P < 0.05 in each cluster). The metabolic abnormalities were less pronounced in persons with ONAP or affective psychosis.
Our findings suggest that specific metabolic abnormalities related to glucoregulatory processes and proline metabolism are specifically associated with schizophrenia and reflect two different disease-related pathways. Metabolomics, which is sensitive to both genetic and environmental variation, may become a powerful tool in psychiatric research to investigate disease susceptibility, clinical course, and treatment response.
A low level of high density lipoprotein cholesterol (HDL-C) is a powerful risk factor for cardiovascular disease. However, despite the reported key role of apolipo-proteins, specifically, apoA-I, in ...HDL metabolism, lipid molecular composition of HDL particles in subjects with high and low HDL-C levels is currently unknown. Here lipidomics was used to study HDL derived from well-characterized high and low HDL-C subjects. Low HDL-C subjects had elevated triacylglycerols and diminished lysophosphatidylcholines and sphingomyelins. Using information about the lipid composition of HDL particles in these two groups, we reconstituted HDL particles in silico by performing large-scale molecular dynamics simulations. In addition to confirming the measured change in particle size, we found that the changes in lipid composition also induced specific spatial distributions of lipids within the HDL particles, including a higher amount of triacylglycerols at the surface of HDL particles in low HDL-C subjects. Our findings have important implications for understanding HDL metabolism and function. For the first time we demonstrate the power of combining molecular profiling of lipoproteins with dynamic modeling of lipoprotein structure.
Due to the growing prevalence of type 2 diabetes, new dietary solutions are needed to help improve glucose and lipid metabolism in persons at high risk of developing the disease. Herein we ...investigated the effects of low-insulin-response grain products, fatty fish, and berries on glucose metabolism and plasma lipidomic profiles in persons with impaired glucose metabolism.
Altogether 106 men and women with impaired glucose metabolism and with at least two other features of the metabolic syndrome were included in a 12-week parallel dietary intervention. The participants were randomized into three diet intervention groups: (1) whole grain and low postprandial insulin response grain products, fatty fish three times a week, and bilberries three portions per day (HealthyDiet group), (2) Whole grain enriched diet (WGED) group, which includes principally the same grain products as group (1), but with no change in fish or berry consumption, and (3) refined wheat breads (Control). Oral glucose tolerance, plasma fatty acids and lipidomic profiles were measured before and after the intervention. Self-reported compliance with the diets was good and the body weight remained constant. Within the HealthyDiet group two hour glucose concentration and area-under-the-curve for glucose decreased and plasma proportion of (n-3) long-chain PUFAs increased (False Discovery Rate p-values <0.05). Increases in eicosapentaenoic acid and docosahexaenoic acid associated curvilinearly with the improved insulin secretion and glucose disposal. Among the 364 characterized lipids, 25 changed significantly in the HealthyDiet group, including multiple triglycerides incorporating the long chain (n-3) PUFA.
The results suggest that the diet rich in whole grain and low insulin response grain products, bilberries, and fatty fish improve glucose metabolism and alter the lipidomic profile. Therefore, such a diet may have a beneficial effect in the efforts to prevent type 2 diabetes in high risk persons.
ClinicalTrials.gov NCT00573781.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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