Availability Of Fatty Acids Research Articles

Effects of abomasal infusions of fatty acids and 1-carbon donors on apparent fatty acid digestibility and incorporation into milk fat in cows

Our primary objective was to determine the effects of the abomasal infusion of 16-carbon (16C) and 22-carbon (22C) fatty acids (FA) on apparent FA digestibility, plasma FA concentrations, and their incorporation into milk fat in cows. Our secondary objective was to study the effects of 1-carbon donors choline and l-serine on these variables. Five rumen-cannulated Holstein cows (214 ± 4.9 d in milk; 3.2 ± 1.1 parity) were enrolled in a 5 × 5 Latin square experiment with experimental periods lasting 6 d. Abomasal infusates consisted of (1) palmitic acid (PA; 98% 16:0 of total fat), (2) PA + choline chloride (PA+CC; 50 g/d of choline chloride), (3) PA + l-serine (PA+S; 170 g/d of l-serine), (4) behenic acid (BA; 92% 22:0 of total fat), and (5) docosahexaenoic acid algal oil (DHA; 47.5% DHA of total fat). Emulsions were formulated to provide 301 g/d of total FA and were balanced to provide a minimum of 40 and 19 g/d of 16:0 and glycerol, respectively, to match the content found in the infused algal oil. Apparent digestibility of FA was highest in DHA, intermediate in PA, and lowest in BA. Digestibility of 16C FA was lowest in BA and highest in PA. The digestibility of 22C FA was highest in DHA relative to BA (99 vs. 58%), whereas 1-carbon donors had no effect on 22C FA digestibility. Plasma 16C FA concentrations were greatest with PA treatment, and 22C FA concentrations were ~3-fold greater in DHA-treated cows relative to all other treatments. Milk fat 16:0 content was highest in PA relative to BA and DHA (e.g., 37 vs. 27% in PA and DHA), whereas the milk yield of 16:0 was higher in PA relative to DHA (i.e., 454 vs. 235 g/d). Similarly, milk 22:0 content and yield were ~10-fold higher in BA relative to all other treatments, whereas DHA treatment resulted in higher content and yield of 22:6 in milk fat relative to all other treatments (41- and 38-fold higher, respectively). Consequently, the content of FA >16C (i.e., preformed) was higher in milk fat from cows infused with BA and DHA relative to PA. De novo FA content in milk did not differ between PA, PA+CC, and PA+S (~16% of milk fat) but was higher in BA and DHA treatments (19 and 21%, respectively). We conclude that FA carbon chain length and degree of saturation affected FA digestibility and availability for absorption as well as their incorporation into milk fat. The abomasal infusion of choline chloride and l-serine did not modify these variables relative to infusing palmitic acid alone.

Mixotrophic cultivation of Chlorella vulgaris in sugarcane molasses preceding nitrogen starvation: Biomass productivity, lipid content, and fatty acid analyses

AbstractIn the present study, a precharacterized oleaginous microalgal species (Chlorella vulgaris) was exploited for its biomass productivity, lipid yield, and fatty acid analysis under mixotrophic and photoautotrophic conditions. For the purpose, the microalgal biomass was raised mixotrophically as well photoautotrophically. For mixotrophic cultivation, molasses was used as additional source of carbon and energy, while for photoautotrophic cultivation, atmospheric CO2 was the sole source of carbon and energy. The microalgal biomass raised thus was then harvested following 5 days of nitrogen starvation. Mixotrophic cultivation depicted remarkably higher biomass productivity (137.43 ± 13.3 mg L−1 day−1) than that of photoautotrophic cultivation (91.57 ± 7.9 mg L−1 day−1). About 39% (w/w) of total lipid content was obtained from the dried biomass raised mixotrophically. Lipidomic analysis of the extracted oil depicted higher concentrations of polyunsaturated fatty acids (palmitic and oleic acids). The significant availability of polyunsaturated fatty acids (60 mg g−1 of dried algal biomass) ensured the production of high quality biofuel.

Apparent Digestibility of Macronutrients and Fatty Acids from Microalgae (Schizochytrium sp.) Fed to Rainbow Trout (Oncorhynchus mykiss): A Potential Candidate for Fish Oil Substitution.

Simple SummaryAquaculture is the world’s fastest growing sector of the global food system. Aquaculture feed producers are seeking substitutes for fishmeal and fish oil to develop more sustainable feeds. Marine microalgae show promise as potential ingredients in aquafeeds; however, the literature lacks data on the digestibility and availability of macronutrients and individual fatty acids for omega 3-rich microalgal biomass, Schizochytrium spp., in rainbow trout. This is an important gap to fill because, among marine microalgae, this species is the most frequently used in fish feed, particularly as a dietary supplement or mixed with other ingredients; digestibility data would guide more judicious inclusion of this microalga biomass. High digestibility of macronutrients, energy and fatty acids showed that Schizochytrium spp. is a high-quality substitute for fish oil and potential candidate as a supplement of LC-PUFA in trout feed with vegetable oils. Digestibility is influenced by temperature and several trials have shown increased macronutrient digestibility with increasing temperature. There is an urgent need to determine the effect of temperature on lipid and fatty acid digestibility. We found that the digestibility of nutrients in rainbow trout maintained at 8 °C or 15 °C was not significantly different. However, the digestibility of DHA omega 3 was significantly higher at 8 °C than at 15 °C.Aquaculture feed formulation has recently turned its focus to reduce the reliance on marine-derived resources and utilise alternative feedstuffs, as an approach to improve the environmental sustainability of the aquaculture sector. The fish oil market is highly volatile, and availability of this commodity is continuously decreasing for use in aquaculture. Currently, a growing number of commercial efforts producing microalgae are providing omega 3-rich oil for sustainable aquaculture feed. This study was focused to determine the nutrient digestibility of a marine microalga, Schizochytrium spp., which is rich in docosahexaenoic acid (DHA) and long-chain polyunsaturated fatty acids (LC-PUFA), as a novel dietary lipid source that could be utilized effectively by rainbow trout (Oncorhynchus mykiss). A whole-cell Schizochytrium spp. biomass was used in the digestibility experiment at two different temperatures, 8 °C and 15 °C. No significant differences were detected between the two temperatures for the apparent digestibility coefficients (ADCs) of the dry matter (94.3 ± 4.9%), total lipids (85.8 ± 0.0%), crude proteins (89.5 ± 1.8%), energy (83.1 ± 1.7%) and fatty acids (85.8 ± 7.5%). The ADCs of the nutrients, energy, DHA and other fatty acids showed that Schizochytrium spp. is a high-quality candidate for fish oil substitution and supplement of LC-PUFA in fish feed with vegetable oils.

Influence of Yeast Products on Modulating Metabolism and Immunity in Cattle and Swine.

Simple SummaryDietary supplementation has been used in order to improve animal growth and health, and reduce the risk of disease for many years. Yeast and yeast products are a group of supplements that have broad applications in livestock production. These benefits include improving milk production, weight gain, and immunity. Recent studies suggest that yeast can have impacts beyond growth and health and may impact metabolism. Available energy is important for immune activation, and therefore any change in metabolism and energy availability may affect immune responses. This paper explores the effects of yeast on energy metabolism and how these changes may influence immune responses in cattle and swine.Nutritional supplementation has been used by livestock producers for many years in order to increase animal performance, improve animal health, and reduce negative effects associated with enteric and/or respiratory pathogens. Supplements such as yeast and yeast-based products have broad applications across many livestock production systems, including poultry, aquaculture, cattle, and swine and have been shown to benefit animal production at various stages. These benefits include improvement in milk production, weight gain and feed conversion, as well as immune function. Initial research into the mode of action for these effects has focused on stimulation of the immune system by the β-glucan fractions of yeast. However, emerging studies have revealed that some of the beneficial effects of yeast products may stem from altering metabolism, including the availability of glucose and fatty acids. These changes in metabolism, and potentially energy availability, may partially explain differences in immune function observed in yeast-supplemented livestock, as the energy demands of an activated immune system are extremely high. Thus, this paper explores the influence of yeast products on metabolism in cattle and swine, and how changes in metabolism and energy availability may contribute to improvements in immune function in supplemented animals.

Bovine Milk-Derived Emulsifiers Increase Triglyceride Absorption in Newborn Formula-Fed Pigs.

Efficient lipid digestion in formula-fed infants is required to ensure the availability of fatty acids for normal organ development. Previous studies suggest that the efficiency of lipid digestion may depend on whether lipids are emulsified with soy lecithin or fractions derived from bovine milk. This study, therefore, aimed to determine whether emulsification with bovine milk-derived emulsifiers or soy lecithin (SL) influenced lipid digestion in vitro and in vivo. Lipid digestibility was determined in vitro in oil-in-water emulsions using four different milk-derived emulsifiers or SL, and the ultrastructural appearance of the emulsions was assessed using electron microscopy. Subsequently, selected emulsions were added to a base diet and fed to preterm neonatal piglets. Initially, preterm pigs equipped with an ileostomy were fed experimental formulas for seven days and stoma output was collected quantitatively. Next, lipid absorption kinetics was studied in preterm pigs given pure emulsions. Finally, complete formulas with different emulsions were fed for four days, and the post-bolus plasma triglyceride level was determined. Milk-derived emulsifiers (containing protein and phospholipids from milk fat globule membranes and extracellular vesicles) showed increased effects on fat digestion compared to SL in an in vitro digestion model. Further, milk-derived emulsifiers significantly increased the digestion of triglyceride in the preterm piglet model compared with SL. Ultra-structural images indicated a more regular and smooth surface of fat droplets emulsified with milk-derived emulsifiers relative to SL. We conclude that, relative to SL, milk-derived emulsifiers lead to a different surface ultrastructure on the lipid droplets, and increase lipid digestion.

Knockdown of the plastid-encoded acetyl-CoA carboxylase gene uncovers functions in metabolism and development.

De novo fatty acid biosynthesis in plants relies on a prokaryotic-type acetyl-CoA carboxylase (ACCase) that resides in the plastid compartment. The enzyme is composed of four subunits, one of which is encoded in the plastid genome, whereas the other three subunits are encoded by nuclear genes. The plastid gene (accD) encodes the β-carboxyltransferase subunit of ACCase and is essential for cell viability. To facilitate the functional analysis of accD, we pursued a transplastomic knockdown strategy in tobacco (Nicotiana tabacum). By introducing point mutations into the translational start codon of accD, we obtained stable transplastomic lines with altered ACCase activity. Replacement of the standard initiator codon AUG with UUG strongly reduced AccD expression, whereas replacement with GUG had no detectable effects. AccD knockdown mutants displayed reduced ACCase activity, which resulted in changes in the levels of many but not all species of cellular lipids. Limiting fatty acid availability caused a wide range of macroscopic, microscopic, and biochemical phenotypes, including impaired chloroplast division, reduced seed set, and altered storage metabolism. Finally, while the mutants displayed reduced growth under photoautotrophic conditions, they showed exaggerated growth under heterotrophic conditions, thus uncovering an unexpected antagonistic role of AccD activity in autotrophic and heterotrophic growth.

Analysis of phosphatidylcholines alterations in human glioblastoma multiform tissues ex vivo

Significant metabolism alteration is accompanying the cell malignization process. Energy metabolism disturbance leads to the activation of de novo synthesis and beta-oxidation processes of lipids and fatty acids in a cancer cell, which becomes an indicator of pathological processes inside the cell. The majority of studies dealing with lipid metabolism alterations in glial tumors are performed using the cell lines in vitro or animal models. However, such conditions do not entirely represent the physiological conditions of cell growth or possible cells natural variability. This work presents the results of the data obtained by applying ambient mass spectrometry to human glioblastoma multiform tissues. By analyzing a relatively large cohort of primary and secondary glioblastoma samples, we identify the alterations in cells lipid composition, which accompanied the development of grade IV brain tumors. We demonstrate that primary glioblastomas, as well as ones developed from astrocytomas, are enriched with mono- and diunsaturated phosphatidylcholines (PC 26:1, 30:2, 32:1, 32:2, 34:1, 34:2). Simultaneously, the saturated and polyunsaturated phosphatidylcholines and phosphatidylethanolamines decrease. These alterations are obviously linked to the availability of the polyunsaturated fatty acids and activation of the de novo lipid synthesis and beta-oxidation pathways under the anaerobic conditions in the tumor core.

Lipid-induced S-palmitoylation as a Vital Regulator of Cell Signaling and Disease Development

Lipid metabolites are emerging as pivotal regulators of protein function and cell signaling. The availability of intracellular fatty acid is tightly regulated by glycolipid metabolism and may affect human body through many biological mechanisms. Recent studies have demonstrated palmitate, either from exogenous fatty acid uptake or de novo fatty acid synthesis, may serve as the substrate for protein palmitoylation and regulate protein function via palmitoylation. Palmitoylation, the most-studied protein lipidation, encompasses the reversible covalent attachment of palmitate moieties to protein cysteine residues. It controls various cellular physiological processes and alters protein stability, conformation, localization, membrane association and interaction with other effectors. Dysregulation of palmitoylation has been implicated in a plethora of diseases, such as metabolic syndrome, cancers, neurological disorders and infections. Accordingly, it could be one of the molecular mechanisms underlying the impact of palmitate metabolite on cellular homeostasis and human diseases. Herein, we explore the relationship between lipid metabolites and the regulation of protein function through palmitoylation. We review the current progress made on the putative role of palmitate in altering the palmitoylation of key proteins and thus contributing to the pathogenesis of various diseases, among which we focus on metabolic disorders, cancers, inflammation and infections, neurodegenerative diseases. We also highlight the opportunities and new therapeutics to target palmitoylation in disease development.

Omega-3 versus Omega-6 fatty acid availability is controlled by hydrophobic site geometries of phospholipase A2s

Human phospholipase A2s (PLA2) constitute a superfamily of enzymes that hydrolyze the sn-2 acyl-chain of glycerophospholipids, producing lysophospholipids and free fatty acids. Each PLA2 enzyme type contributes to specific biological functions based on its expression, subcellular localization, and substrate specificity. Among the PLA2 superfamily, the cytosolic cPLA2 enzymes, calcium-independent iPLA2 enzymes, and secreted sPLA2 enzymes are implicated in many diseases, but a central issue is the preference for double-bond positions in polyunsaturated fatty acids (PUFAs) occupying the sn-2 position of membrane phospholipids. We demonstrate that each PLA2 has a unique preference between the specific omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the omega-6 arachidonic acid (AA), which are the precursors of most proinflammatory and anti-inflammatory or resolving eicosanoids and related oxylipins. Surprisingly, we discovered that human cPLA2 selectively prefers AA, whereas iPLA2 prefers EPA, and sPLA2 prefers DHA as substrate. We determined the optimal binding of each phospholipid substrate in the active site of each PLA2 to explain these specificities. To investigate this, we utilized recently developed lipidomics-based LC-MS/MS and GC/MS assays to determine the sn-2 acyl chain specificity in mixtures of phospholipids. We performed μs timescale molecular dynamics (MD) simulations to reveal unique active site properties, especially how the precise hydrophobic cavity accommodation of the sn-2 acyl chain contributes to the stability of substrate binding and the specificity of each PLA2 for AA, EPA, or DHA. This study provides the first comprehensive picture of the unique substrate selectivity of each PLA2 for omega-3 and omega-6 fatty acids.

Stearoyl-CoA Desaturase-Mediated Monounsaturated Fatty Acid Availability Supports Humoral Immunity

SUMMARYImmune cells can metabolize glucose, amino acids, and fatty acids (FAs) to generate energy. The roles of different FA species and their impacts on humoral immunity remain poorly understood. Here, we report that proliferating B cells require monounsaturated FAs (MUFAs) to maintain mitochondrial metabolism and mTOR activity and to prevent excessive autophagy and endoplasmic reticulum (ER) stress. Furthermore, B cell-extrinsic stearoyl-CoA desaturase (SCD) activity generates MUFA to support early B cell development and germinal center (GC) formation in vivo during immunization and influenza infection. Thus, SCD-mediated MUFA production is critical for humoral immunity.

The Role of Mitochondrial Fat Oxidation in Cancer Cell Proliferation and Survival.

Tumors remodel their metabolism to support anabolic processes needed for replication, as well as to survive nutrient scarcity and oxidative stress imposed by their changing environment. In most healthy tissues, the shift from anabolism to catabolism results in decreased glycolysis and elevated fatty acid oxidation (FAO). This change in the nutrient selected for oxidation is regulated by the glucose-fatty acid cycle, also known as the Randle cycle. Briefly, this cycle consists of a decrease in glycolysis caused by increased mitochondrial FAO in muscle as a result of elevated extracellular fatty acid availability. Closing the cycle, increased glycolysis in response to elevated extracellular glucose availability causes a decrease in mitochondrial FAO. This competition between glycolysis and FAO and its relationship with anabolism and catabolism is conserved in some cancers. Accordingly, decreasing glycolysis to lactate, even by diverting pyruvate to mitochondria, can stop proliferation. Moreover, colorectal cancer cells can effectively shift to FAO to survive both glucose restriction and increases in oxidative stress at the expense of decreasing anabolism. However, a subset of B-cell lymphomas and other cancers require a concurrent increase in mitochondrial FAO and glycolysis to support anabolism and proliferation, thus escaping the competing nature of the Randle cycle. How mitochondria are remodeled in these FAO-dependent lymphomas to preferably oxidize fat, while concurrently sustaining high glycolysis and increasing de novo fatty acid synthesis is unclear. Here, we review studies focusing on the role of mitochondrial FAO and mitochondrial-driven lipid synthesis in cancer proliferation and survival, specifically in colorectal cancer and lymphomas. We conclude that a specific metabolic liability of these FAO-dependent cancers could be a unique remodeling of mitochondrial function that licenses elevated FAO concurrent to high glycolysis and fatty acid synthesis. In addition, blocking this mitochondrial remodeling could selectively stop growth of tumors that shifted to mitochondrial FAO to survive oxidative stress and nutrient scarcity.

Histone acylation marks respond to metabolic perturbations and enable cellular adaptation

Acetylation is the most studied histone acyl modification and has been recognized as a fundamental player in metabolic gene regulation, whereas other short-chain acyl modifications have only been recently identified, and little is known about their dynamics or molecular functions at the intersection of metabolism and epigenetic gene regulation. In this study, we aimed to understand the link between nonacetyl histone acyl modification, metabolic transcriptional regulation, and cellular adaptation. Using antibodies specific for butyrylated, propionylated, and crotonylated H3K23, we analyzed dynamic changes of H3K23 acylation upon various metabolic challenges. Here, we show that H3K23 modifications were highly responsive and reversibly regulated by nutrient availability. These modifications were commonly downregulated by the depletion of glucose and recovered based on glucose or fatty acid availability. Depletion of metabolic enzymes, namely, ATP citrate lyase, carnitine acetyltransferase, and acetyl-CoA synthetase, which are involved in Ac-CoA synthesis, resulted in global loss of H3K23 butyrylation, crotonylation, propionylation, and acetylation, with a profound impact on gene expression and cellular metabolic states. Our data indicate that Ac-CoA/CoA and central metabolic inputs are important for the maintenance of histone acylation. Additionally, genome-wide analysis revealed that acyl modifications are associated with gene activation. Our study shows that histone acylation acts as an immediate and reversible metabolic sensor enabling cellular adaptation to metabolic stress by reprogramming gene expression.

Effects of Different Processing Treatments on Almond (Prunus dulcis) Bioactive Compounds, Antioxidant Activities, Fatty Acids, and Sensorial Characteristics.

Almond is one of the most commonly consumed nuts worldwide, with health benefits associated with availability of bioactive compounds and fatty acids. Almond is often eaten raw or after some processing steps. However, the latter can positively or negatively influence chemical and sensorial attributes of almonds. This work was carried out to assess the effects of two processing treatments, namely; roasting and blanching on (i) contents of bioactive compounds, (ii) contents of fatty acids (3) antioxidant activities (4), sensorial characteristics of four neglected Portuguese almond cultivars (Casanova, Molar, Pegarinhos and Refêgo) and two foreign cultivars (Ferragnès and Glorieta). Results showed that in general, levels of bioactive compounds and antioxidant activities increased with roasting and decreased with blanching. Fatty acid profiles of raw kernels of all cultivars were generally identical although Refêgo exhibited a high content of α-linolenic acid. Following roasting and blanching, content of polyunsaturated fatty acids increased while saturated fatty acids, monounsaturated fatty acids and several health lipid indices decreased. Roasting positively affected perception of skin color and sweetness of Ferragnès and Glorieta as well as skin roughness of Molar and Pegarinhos. Blanching on the other hand led to positive changes in textural properties of Refêgo and Pegarinhos. This study reveals the nutritive benefits of consuming neglected almond cultivars in Portugal, and the novel data reported here could be of interest to growers, processing companies and consumers.

Acyl-CoA Synthetase Long Chain Family Inhibition with Triacsin C Inhibits Multiple Myeloma Cell Proliferation and Survival

Multiple myeloma (MM) is defined by the clonal expansion of malignant plasma cells in the bone marrow (BM) and has a 5-year survival rate of 50% (Siegel el al. 2018, Cancer J. Clin.). MM remains incurable due to the development of resistance to current chemotherapies; therefore, it is paramount to investigate novel treatments and the mechanisms of drug resistance in MM cells. Interestingly, obesity correlates with increased incidence of MM and high body mass index correlates with a poor treatment response (Marinac et al. 2019, JNCI Cancer Spectr, Groß et al. 2017, Oncotarget). Obesity is a major risk factor for many cancers, however, given the complexity of obesity, there are an array of mechanisms by which obesity may support tumor cells. Studies of obesity and MM are mainly at the epidemiological level and have not extensively explored the mechanism of this relationship. Therefore, there is a critical need to understand how obesity contributes to support cancers such as MM. Possible mechanisms may be through the increased availability of free fatty acids or through other factors that are found in obese patients. We hypothesize that lipid metabolism contributes to obesity-linked cancers such as MM. Recently, changes in lipid metabolism have been shown to support the proliferation, migration and the development of drug resistance in other blood cancers such as acute myeloid leukemia (Tabe et al. 2017, Cancer Res, Tabe et al. 2018, Sci. Reports) and solid tumors such as breast (Wang et al. 2017, JCI Insights) and prostate (Mitra et al. 2017, BMC Cancer) cancer. However, the role of lipid metabolism in MM cells has been understudied. Therefore, we hypothesized that genes within the Hallmark Fatty Acid Metabolism gene set (https://www.gsea-msigdb.org) would be differentially expressed between healthy patients and those with MM. We mined the clinical data (GSE6477, Chng et al. 2007, Cancer Res.) and found that transcripts of an enzyme critical for lipid metabolism, acyl-CoA synthetase long chain member 1 (ACSL1), was significantly downregulated (Figure 1A, Log2(Fold Change)=-2.33, adjusted p value=1.64*10-5, false discovery rate) in patients with newly diagnosed MM relative to normal plasma cells. Therefore, we hypothesized that ACSL1 may act as a tumor suppressor in MM. In order to test the role of the ACSL family as tumor suppressors, we treated human (MM1.S, OPM2 and RPMI-8226) and mouse myeloma (5TGM1) cell lines with an inhibitor (Triacsin C, TriC) of four of the five human acyl-CoA synthetase long chain family members (ACSL1,3,4 and 5). Contrary to our hypothesis, TriC treatment significantly decreased MM cell proliferation (Figure 1B, p<0.0001, One-way ANOVA Tukey's multiple comparisons test is used throughout unless otherwise noted), increased apoptosis (Figure 1C, p<0.001) and caused G0 arrest (Figure1D, p<0.0001) in a dose-dependent manner. Motivated to understand if TriC's toxicity was due to changes in metabolic dynamics, MM1.S cells were treated with 1 μM TriC for 30 minutes and subjected to a metabolic flux assay (Seahorse XF, Agilent). TriC treatment significantly reduced ATP-dependent respiration from fatty acid oxidation (FAO) (Figure 1F, p<0.0001 Student's t-test) and increased proton leak (p<0.0001). Taken together, our data demonstrate that TriC-mediated ACSL inhibition in MM cells decreases proliferation, induces G0 arrest, apoptosis and decreases FAO-dependent respiration and mitochondrial function. It is unclear what ACSL family member is responsible for the phenotype we report here. To address these questions, future studies will focus on genetically targeting individual ACSL family members and characterizing the lipidomic profile of MM ACSL mutants. Our data also suggests that fatty acids are used as an energy source, therefore we will explore how FAO contributes to MM cell proliferation and survival. Disclosures No relevant conflicts of interest to declare.

Analysis of oxylipins to differentiate between organic and conventional UHT milks

Nowadays, there is a strong interest in analytical approaches for assessing organic farming practices. Here, we propose that oxylipins, a group of oxidised metabolites derived from various polyunsaturated fatty acids, could be promising biomarkers for organic milk assessment because their biosynthesis is modulated by both precursor fatty acid availability and physiological or pathological status. Thus, we determined 31 fatty acids, 53 triacylglycerols and 37 oxylipins in one hundred commercial UHT milks by chromatographic methods coupled to mass spectrometry. Of these, 52 milks were conventional (34 whole milk, 11 semi-skimmed milk and 7 skimmed milk) and 48 were organic (31 whole milk, 11 semi-skimmed milk and 6 skimmed milk). Several oxylipins (8-HEPE, 5-HEPE, 11-HEPE, 9-HEPE, 18-HEPE, 9-HOTrE, 13-HOTrE, 12,13-DiHODE and 15,16-DiHODE) could distinguish between organic and conventional milks. Within these oxylipins, arachidonic and linoleic acid derived do not correlate with their fatty acid precursors; therefore these oxylipins could be promising as not only diet-dependent biomarkers for organic milk assessment.

Intrapopulation variability in a functional trait: Susceptibility ofDaphniato limitation by dietary fatty acids

AbstractFunctional traits are measurable characteristics of an organism that have an impact on its fitness. Variation in functional traits between and among species has been suggested to represent the basis for competition and selection, thus allowing for evolution in natural populations.In freshwater ecosystems, the availability of essential polyunsaturated fatty acids (PUFAs), in particular ω3‐ and ω6‐PUFAs, determines the food quality of phytoplankton for the herbivorous zooplanktonDaphnia, an unselective filter feeder. The content of such essential PUFAs in the phytoplankton is thus a functional phytoplankton trait affecting the trophic transfer efficiency and dynamics at the pelagic plant–herbivore interface.In turn, the susceptibility of consumers to become limited by the availability of essential PUFAs is a fitness‐determining trait ofDaphniagenotypes, and variability of this herbivore trait may thus affect the daphnids’ intrapopulation competition. To estimate the intrapopulation variation in susceptibility, we isolated clonal lines ofDaphnia longispinafrom a natural population and compared the strength of their limitation by dietary PUFA availability via standardised laboratory growth assays. We used a liposome supplementation technique to enrich a PUFA‐poor green alga with essential ω3‐ and ω6‐PUFAs and determined juvenile somatic growth rate of differentD. longispinagenotypes as a fitness proxy.As expected,D. longispinagenotypes that coexisted in a natural population differed markedly in their specific patterns of susceptibility to dietary PUFA availability. On average, theD. longispinapopulation was more strongly susceptible to limitations in the availability of the ω6‐PUFA arachidonic acid (20:4ω6) than to limitations in the availability of ω3‐PUFAs α‐linolenic acid (18:3ω3) and eicosapentaenoic acid (20:5ω3).The ability to cope with PUFA limitation is thus a crucial trait that can probably affect intraspecific competition andDaphniapopulation structure. Therefore, we suggest that such intrapopulation variation in susceptibility to absence of dietary PUFAs might be one of the driving forces of natural selection and local adaptation among freshwater zooplankton.

Tuning fatty acid oxidation in skeletal muscle with dietary fat and exercise.

Both the consumption of a diet rich in fatty acids and exercise training result in similar adaptations in several skeletal muscle proteins. These adaptations are involved in fatty acid uptake and activation within the myocyte, the mitochondrial import of fatty acids and further metabolism of fatty acids by β-oxidation. Fatty acid availability is repeatedly increased postprandially during the day, particularly during high dietary fat intake and also increases during, and after, aerobic exercise. As such, fatty acids are possible signalling candidates that regulate transcription of target genes encoding proteins involved in muscle lipid metabolism. The mechanism of signalling might be direct or indirect targeting of peroxisome proliferator-activated receptors by fatty acid ligands, by fatty acid-induced NAD+-stimulated activation of sirtuin 1 and/or fatty acid-mediated activation of AMP-activated protein kinase. Lactate might also have a role in lipid metabolic adaptations. Obesity is characterized by impairments in fatty acid oxidation capacity, and individuals with obesity show some rigidity in increasing fatty acid oxidation in response to high fat intake. However, individuals with obesity retain improvements in fatty acid oxidation capacity in response to exercise training, thereby highlighting exercise training as a potential method to improve lipid metabolic flexibility in obesity.

Nicotinic acid receptor agonists impair myocardial contractility by energy starvation.

Nicotinic acid receptor agonists have previously been shown to cause acute reductions in cardiac contractility. We sought to uncover the changes in cardiac metabolism underlying these alterations in function. In nine humans, we recorded cardiac energetics and function before and after a single oral dose of nicotinic acid using cardiac MRI to demonstrate contractile function and Phosphorus-31 (31 P) magnetic resonance spectroscopy to demonstrate myocardial energetics. Nicotinic Acid 400mg lowered ejection fraction by 4% (64±8% to 60±7%, P=.03), and was accompanied by a fall in phosphocreatine/ATP ratio by 0.4 (2.2±0.4 to 1.8±0.1, P=.04). In four groups of eight Wistar rats, we used pyruvate dehydrogenase (PDH) flux studies to demonstrate changes in carbohydrate metabolism induced by the nicotinic acid receptor agonist, Acipimox, using hyperpolarized Carbon-13 (13 C) magnetic resonance spectroscopy. In rats which had been starved overnight, Acipimox caused a fall in ejection fraction by 7.8% (67.5±8.9 to 60±3.1, P=.03) and a nearly threefold rise in flux through PDH (from 0.182±0.114 to 0.486±0.139, P=.002), though this rise did not match pyruvate dehydrogenase flux observed in rats fed carbohydrate rich chow (0.726±0.201). In fed rats, Acipimox decreased pyruvate dehydrogenase flux (to 0.512±0.13, P=.04). Concentration of plasma insulin fell by two-thirds in fed rats administered Acipimox (from 1695±891ng/L to 550±222ng/L, P=.005) in spite of glucose concentrations remaining the same. In conclusion, we demonstrate that nicotinic acid receptor agonists impair cardiac contractility associated with a decline in cardiac energetics and show that the mechanism is likely a combination of reduced fatty acid availability and a failure to upregulate carbohydrate metabolism, essentially starving the heart of fuel.

Lake restoration influences nutritional quality of algae and consequently Daphnia biomass

Food quality is one of the key factors influencing zooplankton population dynamics. Eutrophication drives phytoplankton communities toward the dominance of cyanobacteria, which means a decrease in the availability of sterols and long-chain polyunsaturated fatty acids (EPA and DHA). The effects of different restoration measures on the nutritional quality of the phytoplankton community and subsequent impacts on zooplankton biomass have rarely been considered. We analyzed the nutritional quality of phytoplankton in the eutrophic Lake Vesijärvi in southern Finland over a 37-year period, and studied the impacts of two restoration measures, biomanipulation and hypolimnetic aeration, on the abundance of high-quality phytoplankton. We found that biomanipulation had a positive impact on the abundance of taxa synthesizing sterols, EPA, and DHA and, concurrently, on the biomass of the keystone species Daphnia. In contrast, hypolimnetic aeration did not result in such a beneficial outcome, manifested as a decrease in the abundance of Daphnia and frequent phytoplankton blooms dominated by cyanobacteria suggesting reduction in the nutritional quality of food for Daphnia. Our analysis shows that the determination of the nutritional value of algae and the contribution of essential fatty acids and sterols is an effective method to evaluate the success of various restoration measures.

Metabolic Flexibility of Mitochondria Plays a Key Role in Balancing Glucose and Fatty Acid Metabolism in the Diabetic Heart.

In order to meet its energy requirements, the heart has the intrinsic capability to metabolize a wide range of energy substrates. In normal conditions, the heart favors fatty acids as the main energetic substrate, followed by carbohydrates, ketone bodies, and, lastly, amino acids (1,2). Yet, the myocardium is able to dynamically switch its metabolism according to substrate availability, in order to attempt to guarantee an efficient pumping function in virtually any scenario (2,3). Mechanistically, this phenomenon seems to be possible, as the different substrates available in the heart compete as source of energy, making the final choice essentially based on the relative substrate concentrations. In a seminal Nature article published in 1961, Schipp et al. (4) demonstrated for the first time that increasing fatty acid availability resulted in a marked inhibition of glucose oxidation. Overall, the high flexibility in selecting the most suitable fuel is considered a fingerprint of a healthy myocardium (1). Accordingly, an impaired metabolic flexibility is strongly linked to cardiac damage and dysfunction (2). In the presence of diverse pathological conditions, cardiac metabolism might lose the ability to use some substrates. Whether this phenomenon is deleterious or actually denotes an adaptive response of the myocardium to keep its metabolic rate remains controversial. However, clarifying this aspect is of crucial importance, especially in order to design new therapeutic strategies. In this context, diabetic cardiomyopathy is one of the most critical knots to untie. In diabetes, despite the hyperglycemic status, a reduced capability to use glucose by myocardium has been reported (5,6). However, whether such impairment in glucose oxidization is an adaptive or maladaptive response of the diabetic heart remains to be elucidated. The matter is highly debated, despite recent evidence …