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1.
Industrial uses of phospholipases: current state and future applications.
Cerminati, S, Paoletti, L, Aguirre, A, Peirú, S, Menzella, HG, Castelli, ME
Applied microbiology and biotechnology. 2019;(6):2571-2582
Abstract
Phospholipids play a central role in all living organisms. Phospholipases, the enzymes aimed at modifying phospholipids, are consequently widespread in nature and play diverse roles, from lipid metabolism and cellular signaling in eukaryotes to virulence and nutrient acquisition in microbes. Phospholipases catalyze the hydrolysis of one or more ester or phosphodiester bonds of glycerophospholipids. The use of phospholipases with industrial purposes has constantly increased over the last 30 years. This demand is rapidly growing given the ongoing improvements in protein engineering and the reduction of enzymes manufacturing costs, making them suitable for industrial use. Here, a general overview of phopholipases A, B, C, and D and their industrial application is presented along with potential new uses for these enzymes. We draw attention to commercial phospholipases used to improve the emulsifying properties of products in the baking, egg, and dairy industries. On the other hand, the improvement of oil degumming by phospholipases is thoroughly analyzed. Moreover, recent developments in enzymatic biodiesel production and the use of phospholipases for the synthesis of phospholipids with pharmaceutical or nutritional value are reviewed.
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Eight-week hempseed oil intervention improves the fatty acid composition of erythrocyte phospholipids and the omega-3 index, but does not affect the lipid profile in children and adolescents with primary hyperlipidemia.
Del Bo', C, Deon, V, Abello, F, Massini, G, Porrini, M, Riso, P, Guardamagna, O
Food research international (Ottawa, Ont.). 2019;:469-476
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Abstract
Children affected by primary hyperlipidemia have a high risk of developing cardiovascular diseases (CVDs) during adulthood. Several studies have reported a positive association between the intake of polyunsaturated fatty acids (PUFAs) and improvements in lipid markers and CVD risk. Dietary supplements may represent a potential strategy in the management of hyperlipidemia. In this context, the effectiveness of hempseed oil (HSO) rich in PUFAs (particularly linoleic acid (LA) and α-linolenic acid (ALA)) in the modulation of hyperlipidemia has been poorly investigated. The present pilot study aimed to explore the impact of HSO supplementation on the serum lipid profile and fatty acid (FA) composition of red blood cells (RBCs) in children and adolescents with primary hyperlipidemia. A randomized, 8 week long, parallel dietary intervention study was performed. Thirty-six hyperlipidemic probands (6-16 years) on diet therapy were randomized into two groups: the HSO group, receiving 3 g of HSO providing 1.4 g of LA and 0.7 g/day of ALA, and the control group. Both groups received specific dietary guidelines. Before and after the intervention, blood samples were collected and the serum lipid profile, FA composition of RBCs and omega-3-index were analyzed. Eight weeks of supplementation with HSO significantly (p < .01) reduced the RBC content of total saturated and monounsaturated FAs (-5.02 ± 7.94% and - 2.12 ± 2.23%, respectively), increased the levels of total n-3 and n-6 PUFAs (+1.57 ± 1.96% and + 5.39 ± 7.18%, respectively) and the omega-3 index (+1.18 ± 1.42%), but failed to affect the serum lipid profile compared to the control group. In conclusion, our findings seem to support the contribution of HSO supplementation in improving the RBC phospholipid composition and omega-3 index, while no effect was observed regarding modulation of the lipid profile. Further controlled studies are necessary to achieve a complete understanding of the effects of HSO in the modulation of hyperlipidemia and CVD risk in this and other target groups.
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Comparing patterns of volatile organic compounds exhaled in breath after consumption of two infant formulae with a different lipid structure: a randomized trial.
Smolinska, A, Baranska, A, Dallinga, JW, Mensink, RP, Baumgartner, S, van de Heijning, BJM, van Schooten, FJ
Scientific reports. 2019;(1):554
Abstract
Infant formulae have been used since decades as an alternative to or a complement to human milk. Human milk, the "gold standard" of infant nutrition, has been studied for its properties in order to create infant formulae that bring similar benefits to the infant. One of the characteristics of milk is the size of the lipid droplets which is known to affect the digestion, gastric emptying and triglyceride metabolism. In the current study a concept infant milk formula with large, phospholipid coating of lipid droplets (mode diameter 3-5 μm; NUTURIS, further described as "active"), was compared to a commercially available formula milk characterised by smaller lipid droplets, further described as "control" (both products derived from Nutricia). We investigated whether we could find an effect of lipid droplet size on volatile compounds in exhaled air upon ingestion of either product. For that purpose, exhaled breath was collected from a group of 29 healthy, non-smoking adult males before ingestion of a study product (baseline measurements, T0) and at the following time points after the test meal: 30, 60, 120, 180 and 240 min. Volatile organic compounds (VOCs) in breath were detected by gas chromatography-time-of-flight-mass spectrometry. Any differences in the time course of VOCs patterns upon intake of active and control products were investigated by regularised multivariate analysis of variance (rMANOVA). The rMANOVA analysis revealed statistically significant differences in the exhaled breath composition 240 min after ingestion of the active formula compared to control product (p-value < 0.0001), but did not show significant changes between active and control product at any earlier time points. A set of eight VOCs in exhaled breath had the highest contribution to the difference found at 240 minutes between the two formulas. A set of ten VOCs was different between baseline and the two formulae at T240 with p-value < 0.0001. To our knowledge this is the first study that shows the ability of VOCs in exhaled breath to monitor metabolic effects after ingestion of infant formulae with different lipid structure. The statistically significant differences in compound abundance found between active and control formula milk may be related to: (i) specific differences in the digestion, (ii) absorption of lipids and proteins and (iii) assimilation of the products in the gut.
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Fat SIRAH: Coarse-Grained Phospholipids To Explore Membrane-Protein Dynamics.
Barrera, EE, Machado, MR, Pantano, S
Journal of chemical theory and computation. 2019;(10):5674-5688
Abstract
The capability to handle highly heterogeneous molecular assemblies in a consistent manner is among the greatest challenges faced when deriving simulation parameters. This is particularly the case for coarse-grained (CG) simulations in which chemical functional groups are lumped into effective interaction centers for which transferability between different chemical environments is not guaranteed. Here, we introduce the parametrization of a set of CG phospholipids compatible with the latest version of the SIRAH force field for proteins. The newly introduced lipid species include different acylic chain lengths and partial unsaturation, as well as polar and acidic head groups that show a very good reproduction of structural membrane determinants, such as areas per lipid, thickness, order parameter, etc., and their dependence with temperature. Simulation of membrane proteins showed unprecedented accuracy in the unbiased description of the thickness-dependent membrane-protein orientation in systems where this information is experimentally available (namely, the SarcoEndoplasmic Reticulum Calcium-SERCA-pump and its regulator Phospholamban). The interactions that lead to this faithful reproduction can be traced down to the single amino acid-lipid interaction level and show full agreement with biochemical data present in the literature. Finally, the present parametrization is implemented in the GROMACS and AMBER simulation packages facilitating its use by a wide portion of the biocomputing community.
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Using joint models to disentangle intervention effect types and baseline confounding: an application within an intervention study in prodromal Alzheimer's disease with Fortasyn Connect.
van Oudenhoven, FM, Swinkels, SHN, Hartmann, T, Soininen, H, van Hees, AMJ, Rizopoulos, D
BMC medical research methodology. 2019;(1):163
Abstract
BACKGROUND Many prodromal Alzheimer's disease trials collect two types of data: the time until clinical diagnosis of dementia and longitudinal patient information. These data are often analysed separately, although they are strongly associated. By combining the longitudinal and survival data into a single statistical model, joint models can account for the dependencies between the two types of data. METHODS We illustrate the major steps in a joint modelling approach, motivated by data from a prodromal Alzheimer's disease study: the LipiDiDiet trial. RESULTS By using joint models we are able to disentangle baseline confounding from the intervention effect and moreover, to investigate the association between longitudinal patient information and the time until clinical dementia diagnosis. CONCLUSIONS Joint models provide a valuable tool in the statistical analysis of clinical studies with longitudinal and survival data, such as in prodromal Alzheimer's disease trials, and have several added values compared to separate analyses.
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Alzheimer's Disease Composite Score: A Post-Hoc Analysis Using Data from the LipiDiDiet Trial in Prodromal Alzheimer's Disease.
Hendrix, SB, Soininen, H, van Hees, AMJ, Ellison, N, Visser, PJ, Solomon, A, Attali, A, Blennow, K, Kivipelto, M, Hartmann, T
The journal of prevention of Alzheimer's disease. 2019;(4):232-236
Abstract
As research evolves in prodromal AD, the need to validate sufficiently sensitive outcome measures, e.g. the Alzheimer's Disease Composite Score (ADCOMS) is clear. In the LipiDiDiet randomized trial in prodromal AD, cognitive decline in the study population was much less than expected in the timeframe studied. While the primary composite endpoint was insufficiently sensitive to detect a difference in the modified intention to treat population, the per-protocol population showed less decline in the active than the control group, indicating better treatment effects with regular product intake. These results were further strengthened by significant benefits on secondary endpoints of cognition and function, and brain atrophy. The present post-hoc analysis investigated whether ADCOMS could detect a difference between groups in the LipiDiDiet population (138 active, 140 control). The estimated mean change in ADCOMS from baseline (standard error) was 0.085 (0.018) in the active and 0.133 (0.018) in the control group; estimated mean treatment difference -0.048 (95% confidence intervals -0.090, -0.007; p=0.023), or 36% less decline in the active group. This suggests ADCOMS identified the cognitive and functional benefits observed previously, confirming the sensitivity of this composite measure.
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The LipiDiDiet trial: what does it add to the current evidence for Fortasyn Connect in early Alzheimer's disease?
Rasmussen, J
Clinical interventions in aging. 2019;:1481-1492
Abstract
Nutritional factors can influence the risk of developing Alzheimer's disease (AD) and its rate of progression, and there is, therefore, increasing interest in nutrition as a modifiable risk factor for the disease. Synaptic loss is an important feature of early AD, and the formation of new synapses is dependent on key nutritional elements that are known to be deficient in patients with AD. The daily medical food, Souvenaid, contains Fortasyn Connect, a multinutrient combination developed to specifically address these deficiencies, comprising docosahexaenoic acid, eicosapentaenoic acid, uridine monophosphate, choline, phospholipids, selenium, folic acid, and vitamins B12, B6, C, and E. Although yielding heterogeneous findings, clinical studies of Fortasyn Connect provide preliminary evidence of clinically relevant benefits on cognitive outcomes in prodromal and early AD. The LipiDiDiet trial investigated the effects of Fortasyn Connect on cognition and related measures in prodromal AD, and is the first randomized, controlled, double-blind, multicenter trial study of a non-pharmacological intervention in this setting. The primary efficacy endpoint was change over 24 months in a composite score of cognitive performance using a neuropsychological test battery. Fortasyn Connect had no significant effect on this endpoint, but demonstrated a significant benefit on secondary endpoints, including domains of cognition affected by AD (attention, memory, executive function) and hippocampal atrophy, suggesting a potential benefit on disease progression. Other studies have demonstrated benefits for Fortasyn Connect on nutritional markers and levels of plasma homocysteine. Taken together, current evidence indicates that Fortasyn Connect may show benefit on domains of cognition affected by AD and nutritional measures that influence risk factors for its progression; that it has greater potential for benefit earlier rather than later in the disease; and that it is safe and well tolerated, alone or in combination with AD medications. Further research into its potential role in AD management is therefore warranted.
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Chokeberry Juice Containing Polyphenols Does Not Affect Cholesterol or Blood Pressure but Modifies the Composition of Plasma Phospholipids Fatty Acids in Individuals at Cardiovascular Risk.
Pokimica, B, García-Conesa, MT, Zec, M, Debeljak-Martačić, J, Ranković, S, Vidović, N, Petrović-Oggiano, G, Konić-Ristić, A, Glibetić, M
Nutrients. 2019;(4)
Abstract
Chokeberry polyphenols have been suggested to reduce cholesterol and blood pressure and thus protect against cardiovascular diseases (CVD), but the evidence in humans is limited and inconsistent. This randomized double-blinded three-parallel groups trial investigated the changes in various anthropometric and clinical biomarkers, and in plasma phospholipids fatty acids (PPFA) in volunteers at cardiovascular risk after a four-week intervention with 100 mL/day of (1) chokeberry juice with a high-dose of polyphenols (1177.11 mg gallic acid equivalents, GAE); (2) chokeberry juice with a low-dose of polyphenols (294.28 mg GAE) and; (3) a nutritionally matched polyphenol-free placebo drink. Our results indicate that the intake of chokeberry juice containing either the low or the high dose of polyphenols cannot be linked with a reduction in total- and low-density lipoprotein (LDL)cholesterol or in systolic (SBP) and diastolic (DBP) blood pressure in comparison with the consumption of the placebo drink. However, we found evidence of moderate changes in the PPFA, i.e., increased saturated fatty acids (SFA), mostly palmitic acid, and reduced n-6 polyunsaturated fatty acids (PUFA), principally linoleic acid (LA) with the intake of chokeberry against the placebo. These effects may be associated with the polyphenols but we could not differentiate a clear dose-response effect. Further research is still needed to elucidate the contribution of the polyphenolic fraction to the potential cardiovascular effects of the chokeberry and to build up the evidence of its potential benefit via the modulation of PPFA composition.
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Plasma Phospholipid Fatty Acids and Coronary Heart Disease Risk: A Matched Case-Control Study within the Women's Health Initiative Observational Study.
Liu, Q, Matthan, NR, Manson, JE, Howard, BV, Tinker, LF, Neuhouser, ML, Van Horn, LV, Rossouw, JE, Allison, MA, Martin, LW, et al
Nutrients. 2019;(7)
Abstract
BACKGROUND AND AIMS The association of fatty acids with coronary heart disease (CHD) has been examined, mainly through dietary measurements, and has generated inconsistent results due to measurement error. Large observational studies and randomized controlled trials have shown that plasma phospholipid fatty acids (PL-FA), especially those less likely to be endogenously synthesized, are good biomarkers of dietary fatty acids. Thus, PL-FA profiles may better predict CHD risk with less measurement error. METHODS We performed a matched case-control study of 2428 postmenopausal women nested in the Women's Health Initiative Observational Study. Plasma PL-FA were measured using gas chromatography and expressed as molar percentage (moL %). Multivariable conditional logistic regression was used to calculate odds ratios (95% CIs) for CHD associated with 1 moL % change in PL-FA. RESULTS Higher plasma PL long-chain saturated fatty acids (SFA) were associated with increased CHD risk, while higher n-3 polyunsaturated fatty acids (PUFA) were associated with decreased risk. No significant associations were observed for very-long-chain SFA, monounsaturated fatty acids (MUFA), PUFA n-6 or trans fatty acids (TFA). Substituting 1 moL % PUFA n-6 or TFA with an equivalent proportion of PUFA n-3 were associated with lower CHD risk. CONCLUSIONS Higher plasma PL long-chain SFA and lower PUFA n-3 were associated with increased CHD risk. A change in diet by limiting foods that are associated with plasma PL long-chain SFA and TFA while enhancing foods high in PUFA n-3 may be beneficial in CHD among postmenopausal women.
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10.
Rab39a and Rab39b Display Different Intracellular Distribution and Function in Sphingolipids and Phospholipids Transport.
Gambarte Tudela, J, Buonfigli, J, Luján, A, Alonso Bivou, M, Cebrián, I, Capmany, A, Damiani, MT
International journal of molecular sciences. 2019;(7)
Abstract
Rab GTPases define the identity and destiny of vesicles. Some of these small GTPases present isoforms that are expressed differentially along developmental stages or in a tissue-specific manner, hence comparative analysis is difficult to achieve. Here, we describe the intracellular distribution and function in lipid transport of the poorly characterized Rab39 isoforms using typical cell biology experimental tools and new ones developed in our laboratory. We show that, despite their amino acid sequence similarity, Rab39a and Rab39b display non-overlapping intracellular distribution. Rab39a localizes in the late endocytic pathway, mainly at multivesicular bodies. In contrast, Rab39b distributes in the secretory network, at the endoplasmic reticulum/cis-Golgi interface. Therefore, Rab39a controls trafficking of lipids (sphingomyelin and phospholipids) segregated at multivesicular bodies, whereas Rab39b transports sphingolipids biosynthesized at the endoplasmic reticulum-Golgi factory. Interestingly, lyso bis-phosphatidic acid is exclusively transported by Rab39a, indicating that both isoforms do not exert identical functions in lipid transport. Conveniently, the requirement of eukaryotic lipids by the intracellular pathogen Chlamydia trachomatis rendered useful for dissecting and distinguishing Rab39a- and Rab39b-controlled trafficking pathways. Our findings provide comparative insights about the different subcellular distribution and function in lipid transport of the two Rab39 isoforms.