PNPLA1 knockdown inhibits esterification of γ-linolenic acid to ceramide 1 in differentiated keratinocytes.

Patatin-like phospholipase domain-containing 1 (PNPLA1) is crucial in the esterification of linoleic acid (LA; 18:2n-6) to ω-hydroxy fatty acids (FA) of ceramide 1 (Cer1), the major barrier lipid of the differentiated epidermis. We previously reported that γ-linolenic acid (GLA; 18:3n-6) as well as LA is esterified to Cer1 subspecies with sphingosine (d18:1) or eicosasphingosine (d20:1) amide-linked to two different ω-hydroxy FA (30wh:0; 32wh:1). Here, we further investigated whether PNPLA1 is also responsible for esterification of GLA to these Cer1 subspecies in normal human keratinocytes (NHK). As late/terminal differentiation was induced in NHK, PNPLA1 and differentiation markers were expressed, and LA-esterified Cer1 subspecies (18:2n-6/C30wh:0 or C32wh:0/d18:1; 18:2n-6/C32wh:0/d20:1) were detected, which were further increased with LA treatment. GLA-esterified Cer1 subspecies (18:3n-6/C30wh:0 or C32wh:0/d18:1; 18:3n-6/C32wh:0/d20:1) were detected only with GLA treatment. Specific small interfering RNA-mediated knockdown of PNPLA1 (KDP) in differentiated NHK decreased levels of these LA-esterified Cer1 subspecies overall and of involucrin (IVL), a terminal differentiation marker. Moreover, KDP resulted in lesser LA/GLA responses as characterized by more significant decreases in IVL and LA/GLA-esterified Cer1 subspecies overall and an accumulation of non-esterified ω-hydroxy ceramides, their putative precursors; the decrease of 18:3n-6/C32wh:0/d18:1, the predominant GLA-esterified Cer1 subspecies, specifically paralleled the increase of C32wh:0/d18:1, its corresponding precursor. PNPLA1 is responsible for NHK terminal differentiation and also for esterification of GLA to the ω-hydroxy FA of Cer1.

A Walnut-Enriched Diet for 2 Years Changes the Serum Oxylipin Profile in Healthy Older Persons.

BACKGROUND: Oxylipins are products derived from polyunsaturated fatty acids (PUFAs) that play a role in cardiovascular disease and aging. Fish oil-derived n-3 PUFAs promote the formation of anti-inflammatory and vasodilatory oxylipins; however, there are little data on oxylipins derived from α-linolenic acid (C18:3n-3), the primary plant-derived n-3 PUFA. Walnuts are a source of C18:3n-3. OBJECTIVES: To investigate the effect on serum oxylipins of a diet enriched with walnuts at 15% energy (30-60 g/d; 2.6-5.2 g C18:3n-3/d) for 2 y compared to a control diet (abstention from walnuts) in healthy older males and females (63-79 y). METHODS: The red blood cell proportion of α-linolenic acid was determined by gas chromatography as a measure of compliance. Ultra-performance liquid chromatography-tandem mass spectrometry was used to measure serum concentrations of 53 oxylipins in participants randomly assigned to receive the walnut diet (n = 64) or the control diet (n = 51). Two-year concentration changes (final minus baseline) were log-transformed (base log-10) and standardized (mean-centered and divided by the standard deviation of each variable). Volcano plots were then generated (fold change ≥1.5; false discovery rate ≤0.1). For each oxylipin delta surviving multiple testing, we further assessed between-intervention group differences by analysis of covariance adjusting for age, sex, BMI, and the baseline concentration of the oxylipin. RESULTS: The 2-y change in red blood cell C18:3n-3 in the walnut group was significantly higher than that in the control group (P < 0.001). Compared to the control diet, the walnut diet resulted in statistically significantly greater increases in 3 C18:3n-3-derived oxylipins (9-HOTrE, 13-HOTrE, and 12,13-EpODE) and in the C20:5n-3 derived 14,15-diHETE, and greater reductions of the C20:4n-6-derived 5-HETE, 19-HETE, and 5,6-diHETrE. CONCLUSIONS: Long-term walnut consumption changes the serum oxylipin profile in healthy older persons. Our results add novel mechanistic evidence on the cardioprotective effects of walnuts. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01634841.

The protective effects of Gamma-linolenic acid against indomethacin-induced gastric ulcer in rats.

The primary goal of the investigation was to analyse the anti-inflammatory and antioxidant properties of Gamma-linolenic acid (GLA) on rats with indomethacin (IND)-induced gastric ulcers. Thirty rats were divided into five groups: Control, IND (50 mg/kg, p.o.), IND pretreated with GLA 100 mg/kg (p.o. for 14 d), IND pretreated with GLA 150 mg/kg (p.o. for 14 d) and IND pretreated with omeprazole (20 mg/kg, p.o. for 14 d). The stomach tissues were examined to calculate the ulcer index and pH and analyse biochemical markers (prostaglandin E2 (PGE2), cyclooxygenase 1 (COX1), TNF-1, IL-6 and intercellular adhesion molecule-1 (ICAM1)) and oxidative stress parameters (malondialdehyde: (MDA), superoxide dismutase (SOD), glutathione (GSH) and CAT (catalase)) as well as undergo histopathological assessment. GLA 100 and 150 mg/kg showed a protective effect against IND-induced gastric damage. It reduced levels of COX1, TNF-1, IL-6 and ICAM and increased PGE2 levels. GLA also normalised antioxidant function by modulating MDA, SOD, GSH and CAT. GLA intervention protects against IND-induced gastric ulcers by restoring oxidant/antioxidant balance and reducing inflammation.

α-linolenic acid ameliorates pentylenetetrazol-induced neuron apoptosis and neurological impairment in mice with seizures via down-regulating JAK2/STAT3 pathway.

Epilepsy ranks fourth among neurological diseases, featuring spontaneous seizures and behavioral and cognitive impairments. Although anti-epileptic drugs are currently available clinically, 30% of epilepsy patients are still ineffective in treatment, and 52% of patients experience serious adverse reactions. In this work, the neuroprotective effect of α-linolenic acid (ALA, a nutrient) in mice and its potential molecular mechanisms exposed to pentylenetetrazol was assessed. The mice were injected with pentetrazol 37 mg/kg, and ALA was intra-gastrically administered for 40 days. The treatment with ALA significantly reduced the overall frequency of epileptic seizures and improved the behavior impairment and cognitive disorder caused by pentetrazol toxicity. In addition, ALA can not only reduce the apoptosis rate of brain neurons in epileptic mice, but also significantly reduce the content of brain inflammatory factors (IL-6, IL-1, and TNF-α). Furthermore, we predicted that the possible targets of ALA in the treatment of epilepsy were JAK2 and STAT3 through molecular docking. Finally, through molecular docking and Western Blot studies, we revealed the potential mechanism of ALA ameliorates pentylenetetrazol-induced neuron apoptosis and neurological impairment in mice with seizures by downregulating the JAK2/STAT3 pathway. This study aimed to investigate the antiepileptic and neuroprotective effects of ALA, as well as explore its potential mechanisms, through the construction of a chronic ignition mouse model via intraperitoneal PTZ injection. The findings of this research provide crucial scientific support for subsequent clinical application studies in this field.

Alpha-linolenic acid selectively inhibits the contraction of pig coronary arteries mediated through prostanoid TP receptors.

We examined the inhibitory effects of α-linolenic acid (ALA) on the contractions of pig coronary arteries. ALA concentration-dependently inhibited the contractions elicited by U46619 and prostaglandin F2α without affecting those elicited by 80 mM KCl, histamine, acetylcholine, and serotonin. ALA rightward shifted the concentration-response curve of U46619, and Schild plot analysis revealed that ALA competitively antagonized U46619. Furthermore, ALA inhibited the increase in intracellular Ca2+ concentration caused by TP receptor stimulation but not that caused by FP receptor stimulation. These results suggest that ALA behaves as a selective antagonist of TP receptors in coronary arteries.

Improving linolenic acid content in rapeseed oil by overexpression of CsFAD2 and CsFAD3 genes.

With the increasing public attention to the health benefit of polyunsaturated fatty acids (PUFAs) and demand for linolenic acid (C18:3), it is of great significance to increase the C18:3 content in our meal. As an oil crop with high content of C18:3, Camelina sativa has three homologous copies of FAD2 and three homologous copies FAD3. In this study, we seed-specifically overexpressed two Camelina sativa fatty acid desaturase genes, CsFAD2 and CsFAD3, in rapeseed cultivar Zhongshuang 9. The results show that C18:3 content in CsFAD2 and CsFAD3 overexpressed seeds is increased from 8.62% in wild-type (WT) to 10.62-12.95% and 14.54-26.16%, respectively. We crossed CsFAD2 and CsFAD3 overexpression lines, and stable homozygous digenic crossed lines were obtained. The C18:3 content was increased from 8.62% in WT to 28.46-53.57% in crossed overexpression lines. In addition, we found that the overexpression of CsFAD2 and CsFAD3 had no effect on rapeseed growth, development, and other agronomic traits. In conclusion, we successfully generated rapeseed germplasms with high C18:3 content by simultaneously overexpressing CsFAD2 and CsFAD3, which provides a feasible way for breeding high C18:3 rapeseed cultivars. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01445-0.

Urinary metabolomic profiles uncover metabolic pathways in children with asthma.

OBJECTIVE: The prevalence of asthma has gradually increased worldwide in recent years, which has made asthma a global public health problem. However, due to its complexity and heterogeneity, there are a few academic debates on the pathogenic mechanism of asthma. The study of the pathogenesis of asthma through metabolomics has become a new research direction. We aim to uncover the metabolic pathway of children with asthma. METHODS: Liquid chromatography (LC)-mass spectrometry (MS)-based metabolomic analysis was conducted to compare urine metabolic profiles between asthmatic children (n = 30) and healthy controls (n = 10). RESULTS: Orthogonal projections to latent structures-discrimination analysis (OPLS-DA) showed that there were significant differences in metabolism between the asthma group and the control group with three different metabolites screened out, including traumatic acid, dodecanedioic acid, and glucobrassicin, and the levels of traumatic acid and dodecanedioic acid in the urine samples of asthmatic children were lower than those of healthy controls therein. Pathway enrichment analysis of differentially abundant metabolites suggested that α-linolenic acid metabolism was an asthma-related pathway. CONCLUSIONS: This study suggests that there are significant metabolic differences in the urine of asthmatic children and healthy controls, and α-linolenic acid metabolic pathways may be involved in the pathogenesis of asthma.

"Sweet space" strategy for solvent system selection in countercurrent chromatography: A case study on separation of polyunsaturated fatty acids from borage oil.

This study presents a comprehensive strategy for the selection and optimization of solvent systems in countercurrent chromatography (CCC) for the effective separation of compounds. With a focus on traditional organic solvent systems, the research introduces a "sweet space" strategy that merges intuitive understanding with mathematical accuracy, addressing the significant challenges in solvent system selection, a critical bottleneck in the widespread application of CCC. By employing a combination of volume ratios and graphical representations, including both regular and trirectangular tetrahedron models, the proposed approach facilitates a more inclusive and user-friendly strategy for solvent system selection. This study demonstrates the potential of the proposed strategy through the successful separation of gamma-linolenic acid, oleic acid, and linoleic acid from borage oil, highlighting the strategy's effectiveness and practical applicability in CCC separations.

Investigating the effect of wall material and pressure homogenisation on encapsulation parameters and thermal stability in chia seed oil microcapsules.

AIM: To evaluate the effect of different wall material (WM) matrices followed by homogenisation to encapsulate chia seed oil (CSO) using freeze drying technology. METHODS: CSO was encapsulated using three ratios (100/0, 50/50, and 100/0) of two WM matrices: MTS/WPC (modified tapioca starch-whey protein concentrate) and MD/WPC (maltodextrin-whey protein concentrate). The evaluation included encapsulation efficiency (EE), oxidative stability, and α-linolenic acid (ALA) retention. Homogenised microcapsules (-H) were then assessed for storage and thermal stability, along with cumulative oil release. RESULTS: The MD-WPC-H 50/50 microcapsules had superior EE (97.32%), higher ALA retention (60.2%), storage stability (up to 30 days), higher thermal stability (up to 700 °C), and desirable oil release in simulated condition. CONCLUSION: Selecting suitable WM and homogenisation is key for improving EE, storage, thermal stability, and targeted release. The CSO microcapsule can serve as a functional ingredient to improve the quality of diverse food products.

Transcriptome Analysis Reveals the Mechanism by Which Exogenous Melatonin Treatment Delays Leaf Senescence of Postharvest Chinese Kale (Brassica oleracea var. alboglabra).

Melatonin, a pleiotropic small molecule, is employed in horticultural crops to delay senescence and preserve postharvest quality. In this study, 100 µM melatonin treatment delayed a decline in the color difference index h* and a*, maintaining the content of chlorophyll and carotenoids, thereby delaying the yellowing and senescence of Chinese kale. Transcriptome analysis unequivocally validates melatonin's efficacy in delaying leaf senescence in postharvest Chinese kale stored at 20 °C. Following a three-day storage period, the melatonin treatment group exhibited 1637 differentially expressed genes (DEGs) compared to the control group. DEG analysis elucidated that melatonin-induced antisenescence primarily governs phenylpropanoid biosynthesis, lipid metabolism, plant signal transduction, and calcium signal transduction. Melatonin treatment up-regulated core enzyme genes associated with general phenylpropanoid biosynthesis, flavonoid biosynthesis, and the α-linolenic acid biosynthesis pathway. It influenced the redirection of lignin metabolic flux, suppressed jasmonic acid and abscisic acid signal transduction, and concurrently stimulated auxin signal transduction. Additionally, melatonin treatment down-regulated RBOH expression and up-regulated genes encoding CaM, thereby influencing calcium signal transduction. This study underscores melatonin as a promising approach for delaying leaf senescence and provides insights into the mechanism of melatonin-mediated antisenescence in postharvest Chinese kale.

Hepatocyte-Specific Fads1 Overexpression Attenuates Western Diet-Induced Metabolic Phenotypes in a Rat Model.

Fatty acid desaturase 1 (FADS1) is a rate-limiting enzyme in long-chain polyunsaturated fatty acid (LCPUFA) synthesis. Reduced activity of FADS1 was observed in metabolic dysfunction-associated steatotic liver disease (MASLD). The aim of this study was to determine whether adeno-associated virus serotype 8 (AAV8) mediated hepatocyte-specific overexpression of Fads1 (AAV8-Fads1) attenuates western diet-induced metabolic phenotypes in a rat model. Male weanling Sprague-Dawley rats were fed with a chow diet, or low-fat high-fructose (LFHFr) or high-fat high-fructose diet (HFHFr) ad libitum for 8 weeks. Metabolic phenotypes were evaluated at the endpoint. AAV8-Fads1 injection restored hepatic FADS1 protein levels in both LFHFr and HFHFr-fed rats. While AAV8-Fads1 injection led to improved glucose tolerance and insulin signaling in LFHFr-fed rats, it significantly reduced plasma triglyceride (by ~50%) and hepatic cholesterol levels (by ~25%) in HFHFr-fed rats. Hepatic lipidomics analysis showed that FADS1 activity was rescued by AAV8-FADS1 in HFHFr-fed rats, as shown by the restored arachidonic acid (AA)/dihomo-γ-linolenic acid (DGLA) ratio, and that was associated with reduced monounsaturated fatty acid (MUFA). Our data suggest that the beneficial role of AAV8-Fads1 is likely mediated by the inhibition of fatty acid re-esterification. FADS1 is a promising therapeutic target for MASLD in a diet-dependent manner.

Amelioration of nutritional properties of bakery fat using omega-3 fatty acid-rich edible oils: a review.

Bakery products have gained prominence in modern diets due to their convenience and accessibility, often serving as staple meals across diverse regions. However, the fats used in these products are rich in saturated fatty acids and often comprise trans fatty acids, which are considered as a major biomarker for non-communicable diseases like cardiovascular disorders, obesity and diabetes. Additionally, these fats lack the essential omega-3 fatty acids, which are widely known for their therapeutic benefits. They play a major role in lowering the risk of cardiovascular diseases, cancer and diabetes. Thus, there is need for incorporating these essential fatty acids into bakery fats. Nevertheless, fortifying food products with polyunsaturated fatty acids (PUFAs) poses several challenges due to their high susceptibility to oxidation. This oxidative deterioration leads to not only the formation of undesirable flavors, but also a loss of nutritional value in the final products. This review focuses on the development of healthier trans-fat-free bakery fat enriched with omega-3 fatty acids and its effect on the physicochemical, functional, sensory and nutritional properties of bakery fats and products. Further, the role of various technologies like physical blending, enzymatic interesterification and encapsulation to improve the stability of PUFA-rich bakery fat is discussed, where microencapsulation emerged as a novel and effective technology to enhance the stability and shelf life. By preventing deteriorative changes, microencapsulation ensures that the nutritional, physicochemical and sensory properties of food products remain intact. Novel modification methods like interesterification and microencapsulation used for developing PUFA-rich bakery fats have a potential to address the health risks occurring due to consumption of bakery fat having higher amount of saturated and trans fatty acids. © 2023 Society of Chemical Industry.

Enrichment of a fruit-based smoothie beverage with omega-3 fatty acids from microencapsulated chia seed oil.

BACKGROUND: Omega-3 fatty acids are known for their various health benefits. Chia is the richest vegetable source of omega-3 fatty acids. However, its oil is highly susceptible to oxidative deterioration and should be protected for incorporation into food matrices. This work aimed to study the incorporation of different chia oil microcapsules in a powdered beverage, analyzing the effect on the physicochemical characteristics and stability during storage. RESULTS: Different types of microcapsules were obtained: monolayer microcapsules using sodium caseinate and lactose as wall material, and multilayer microcapsules produced through electrostatic deposition using lecithins, chitosan, and chia mucilage as the first, second, and third layers, respectively. The results demonstrated an efficient enrichment of smoothies, with omega-3 fatty acid values ranging from 24.09% to 42.73%, while the original food matrix powder lacked this component. These powder beverages exhibited low moisture content (≤ 2.91%) and low water activity (≤ 0.39). The aerated, packed density and compressibility assays indicated that adding microcapsules made the powders less dense and compressible. The color of the original powdered beverage was not modified. The dispersibility reflected an acceptable instantaneity, reaching the maximum obscuration after 30 s of stirring. The solubility of all the enriched products was higher than 70%, whereas the pH was ~6.8. The contact angle between the powder and liquid indicated an excellent ability to be reconstituted in water. The analysis of the glass transition temperature showed that the storage temperature (25 °C) was adequate. The peroxide value of all the products was low throughout the storage (≤ 1.63 meq peroxide kg-1 of oil at 90 days at 25 ± 2 °C), thus maintaining the quality of the microencapsulated chia oil. CONCLUSIONS: The results suggest that incorporating the monolayer and multilayer chia oil microcapsules that were studied could be a viable strategy for enriching smoothies with the omega-3 fatty acids present in chia seed oil. © 2023 Society of Chemical Industry.

Evening primrose oil enriched with gamma linolenic acid and D/L-alpha tocopherol acetate attenuated carbon tetrachloride-induced hepatic injury model in male rats via TNF-α, IL-1ß, and IL-6 pathway.

The modulatory role of primrose oil (PO) supplementation enriched with γ-linolenic acid and D/L-alpha tocopherol acetate against a carbon tetrachloride (CCl4)-induced liver damage model was assessed in this study. Twenty male Albino rats were divided into four groups. The control group received corn oil orally. The PO group received 10 mg/kg P O orally. The CCl4 group received 2 mL/kg CCl4 orally and PO/CCl4 group; received PO and 2 mL/kg CCl4 orally. The relative liver weight was recorded. Serum liver enzymes, hepatic malondialdehyde (MDA), hepatic reduced glutathione (GSH) and the expression of hepatic tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), and interleukin 6 (IL-6) were assessed. The binding affinities of γ-linolenic acid and D/L-alpha tocopherol constituents with IL-1ß, IL-6 and TNF-α were investigated using molecular docking simulations. Histopathological and electron microscopic examinations of the liver were performed. The results indicated that CCl4 elevated serum liver enzyme and hepatic MDA levels, whereas GSH levels were diminished. The upregulation of IL-1ß, IL-6, and TNF-α gene expressions were induced by CCl4 treatment. The PO/CCl4-treated group showed amelioration of hepatic injury biomarkers and oxidative stress. Restoration of histopathological and ultrastructural alterations while downregulations the gene expressions of TNF-α, IL1-ß and IL-6 were observed. In conclusion, evening primrose oil enriched with γ-linolenic acid and D/L-alpha tocopherol acetate elicited a potential amelioration of CCl4-induced hepatic toxicity.

Exploration of exogenous chlorogenic acid as a potential plant stimulant: enhancing physiochemical properties in Lonicera japonica.

In this study, we applied exogenous chlorogenic acid (CGA) to Lonicera japonica (L. japonica) leaves via foliar sprays every Monday, Wednesday, and Friday for a period of 12 months. Our continuous monitoring over this period revealed a consistent increase in flavonoid levels from the second to the tenth month following the commencement of CGA treatment. This was accompanied by a notable upregulation in the expression of four secondary metabolite-related enzyme genes: LjPAL1, LjPAL2, LjPAL3, and LjISY1. Concurrently, there was a significant enhancement in the total activity of the enzyme phenylalanine ammonia-lyase. The total antioxidant capacity of the plants also showed a marked increase from the third to the seventh month post-treatment initiation, subsequently stabilizing. This increase was also reflected in the elevated activities of key antioxidant enzymes: peroxidase, polyphenol oxidase, and superoxide dismutase. Furthermore, the treatment notably enhanced various indicators of nutrient growth, such as total protein content, total sugar content, and leaf area. Notably, the relative expression of LjTF1, a kind of BZIP transcription factor gene known for its extensive regulatory effects, showed a significant and sustained increase after the start of exogenous CGA treatment. Subsequent metabolomic analysis revealed significant changes in L. japonica metabolites. Specifically, 172 differentially expressed metabolites (DEMs) showed a notable increase (Fold > 1), predominantly in pathways related to nutrient metabolism such as carbohydrate, amino acid, and energy metabolism. Notably, some of the highly expressed DEMs (Fold > 4) are key antioxidants and medicinal components in L. japonica. The experimental findings were in alignment with the metabolomics analysis, indicating that exogenous CGA can act as a stimulant for L. japonica. It promotes the significant accumulation of certain secondary metabolites, enhances nutritive growth, and boosts the plant's total antioxidant capacity. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01435-8.

Lactic acid bacteria-derived γ-linolenic acid metabolites are PPARδ ligands that reduce lipid accumulation in human intestinal organoids.

Gut microbiota regulate physiological functions in various hosts, such as energy metabolism and immunity. Lactic acid bacteria, including Lactobacillus plantarum, have a specific polyunsaturated fatty acid saturation metabolism that generates multiple fatty acid species, such as hydroxy fatty acids, oxo fatty acids, conjugated fatty acids, and trans-fatty acids. How these bacterial metabolites impact host physiology is not fully understood. Here, we investigated the ligand activity of lactic acid bacteria-produced fatty acids in relation to nuclear hormone receptors expressed in the small intestine. Our reporter assays revealed two bacterial metabolites of γ-linolenic acid (GLA), 13-hydroxy-cis-6,cis-9-octadecadienoic acid (γHYD), and 13-oxo-cis-6,cis-9-octadecadienoic acid (γKetoD) activated peroxisome proliferator-activated receptor delta (PPARδ) more potently than GLA. We demonstrate that both γHYD and γKetoD bound directly to the ligand-binding domain of human PPARδ. A docking simulation indicated that four polar residues (T289, H323, H449, and Y473) of PPARδ donate hydrogen bonds to these fatty acids. Interestingly, T289 does not donate a hydrogen bond to GLA, suggesting that bacterial modification of GLA introducing hydroxy and oxo group determines ligand selectivity. In human intestinal organoids, we determined γHYD and γKetoD increased the expression of PPARδ target genes, enhanced fatty acid ß-oxidation, and reduced intracellular triglyceride accumulation. These findings suggest that γHYD and γKetoD, which gut lactic acid bacteria could generate, are naturally occurring PPARδ ligands in the intestinal tract and may improve lipid metabolism in the human intestine.

Bioproduction of n-3 polyunsaturated fatty acids by nematode fatty acid desaturases and elongase in Drosophila melanogaster.

n-3 polyunsaturated fatty acids (n-3 PUFAs), including α-linolenic acid and eicosapentaenoic acid (EPA), are essential nutrients for vertebrates including humans. Vertebrates are n-3 PUFA-auxotrophic; hence, dietary intake of n-3 PUFAs is required for their normal physiology and development. Although fish meal and oil have been utilized as primary sources of n-3 PUFAs by humans and aquaculture, these traditional n-3 PUFA sources are expected to be exhausted because of the increasing consumption requirements of humans. Hence, it is necessary to establish alternative n-3 PUFA sources to reduce the gap between the supply and demand of n-3 PUFAs. Here, we investigated whether insects, which are considered as a novel source of essential nutrients, could store n-3 PUFAs by the forced expression of n-3 PUFA biosynthetic enzymes. We utilized Drosophila as an insect model to generate transgenic strains expressing Caenorhabditis elegans PUFA biosynthetic enzymes and examined their effects on the proportion of fatty acids. The ubiquitous expression of methyl-end desaturase FAT-1 prominently enhanced the proportions of α-linolenic acid, indicating that FAT-1 is useful for metabolic engineering to fortify α-linolenic acid in insect. Furthermore, the ubiquitous expression of nematode front-end desaturases (FAT-3 and FAT-4), PUFA elongase (ELO-1), and FAT-1 led to EPA bioproduction. Hence, nematode PUFA biosynthetic genes may serve as powerful genetic tools for enhancing the proportion of EPA in insects. This study represents the first step toward the establishment of n-3 PUFA-producing insects.

Metabolic, structure-activity characteristics of conjugated linolenic acids and their mediated health benefits.

Conjugated linolenic acid (CLnA) is a mixture of octadecenoic acid with multiple positional and geometric isomers (including four 9, 11, 13-C18:3 isomers and three 8, 10, 12-C18:3 isomers) that is mainly present in plant seeds. In recent years, CLnA has shown many promising health benefits with the deepening of research, but the metabolic characteristics, physiological function differences and mechanisms of different isomers are relatively complex. In this article, the metabolic characteristics of CLnA were firstly reviewed, with focus on its conversion, catabolism and anabolism. Then the possible mechanisms of CLnA exerting biological effects were summarized and analyzed from its own chemical and physical characteristics, as well as biological receptor targeting characteristics. In addition, the differences and mechanisms of different isomers of CLnA in anticancer, lipid-lowering, anti-diabetic and anti-inflammatory physiological functions were compared and summarized. The current results show that the position and cis-trans conformation of conjugated structure endow CLnA with unique physical and chemical properties, which also makes different isomers have commonalities and particularities in the regulation of metabolism and physiological functions. Corresponding the metabolic characteristics of different isomers with precise nutrition strategy will help them to play a better role in disease prevention and treatment. CLnA has the potential to be developed into food functional components and dietary nutritional supplements. The advantages and mechanisms of different CLnA isomers in the clinical management of specific diseases need further study.

Fatty acid correlations with HOMA-IR and HOMA-% ß are differentially dictated by their serum free and total pools and flaxseed oil supplementation.

Objective. The intent of the present study was to test two hypotheses. The primary hypothesis was that there would be differences between blood serum individual free fatty acids (SIFFA) and serum individual total fatty acids (SITFA) in terms of their different relationships (correlations) to each of homeostatic model assessment-individual insulin resistance (HOMA-IR) and homeostatic model assessment-individual insulin resistance-percentage ß-cell function (HOMA-% ß) remaining in human type 2 diabetic patients with pre-flaxseed oil (FXO) and pre-safflower oil (SFO) administration. The secondary hypothesis was that FXO (rich in alpha-linolenic acid, ALA) supplementation would alter these correlations differently in the SIFFA and STIFFA pools in comparison with the placebo SFO (poor in ALA). Methods. Patients were recruited via a newspaper advertisement and two physicians. All patients came to visit 1 and three months later to visit 2. At visit 2, the subjects were randomly assigned (double-blind) to flaxseed or safflower oil (placebo) treatment for three months until visit 3. Results. There were pre-intervention differences in the SIFFA and STIFA pool's relationships with each of HOMA-IR and HOMA-% ß. These relatioships remained either unchanged or became significant after intervention (treatment or placebo). There was a negative correlation found between HOMA-IR and serum free ALA (SFALA) mol % after FXO. Serum total ALA (STALA) mol % had no significant correlations with HOMA-IR and HOMA- % ß before and after flaxseed oil administration. Conclusions. The SIFFA and SITFA pools have different relationships with HOMA-IR and HOMA-% ß for each of pre- and post-intervention. It is concluded that the data support both the primary and the secondary hypotheses indicating that they are correct.

Evaluation of Lipid Extracts from the Marine Fungi Emericellopsis cladophorae and Zalerion maritima as a Source of Anti-Inflammatory, Antioxidant and Antibacterial Compounds.

Marine environments occupy more than 70% of the earth's surface, integrating very diverse habitats with specific characteristics. This heterogeneity of environments is reflected in the biochemical composition of the organisms that inhabit them. Marine organisms are a source of bioactive compounds, being increasingly studied due to their health-beneficial properties, such as antioxidant, anti-inflammatory, antibacterial, antiviral, or anticancer. In the last decades, marine fungi have stood out for their potential to produce compounds with therapeutic properties. The objective of this study was to determine the fatty acid profile of isolates from the fungi Emericellopsis cladophorae and Zalerion maritima and assess the anti-inflammatory, antioxidant, and antibacterial potential of their lipid extracts. The analysis of the fatty acid profile, using GC-MS, showed that E. cladophorae and Z. maritima possess high contents of polyunsaturated fatty acids, 50% and 34%, respectively, including the omega-3 fatty acid 18:3 n-3. Emericellopsis cladophorae and Z. maritima lipid extracts showed anti-inflammatory activity expressed by the capacity of their COX-2 inhibition which was 92% and 88% of inhibition at 200 µg lipid mL-1, respectively. Emericellopsis cladophorae lipid extracts showed a high percentage of inhibition of COX -2 activity even at low concentrations of lipids (54% of inhibition using 20 µg lipid mL-1), while a dose-dependent behaviour was observed in Z. maritima. The antioxidant activity assays of total lipid extracts demonstrated that the lipid extract from E. cladophorae did not show antioxidant activity, while Z. maritima gave an IC20 value of 116.6 ± 6.2 µg mL-1 equivalent to 92.1 ± 4.8 µmol Trolox g-1 of lipid extract in the DPPH• assay, and 101.3 ± 14.4 µg mL-1 equivalent to 106.6 ± 14.8 µmol Trolox g-1 of lipid extract in the ABTS•+ assay. The lipid extract of both fungal species did not show antibacterial properties at the concentrations tested. This study is the first step in the biochemical characterization of these marine organisms and demonstrates the bioactive potential of lipid extracts from marine fungi for biotechnological applications.