Essential Fatty Acid Metabolism Research Articles

Is there a role for essential fatty acids in osteoporosis?

Inflammatory markers are inversely associated with bone density, geometry, and strength in postmenopausal women, and elderly subjects suggesting that osteoporosis is a low-grade systemic inflammatory condition. But glucocorticoids that are potent anti-inflammatory compounds instead of arresting/preventing osteoporosis induce osteoporosis. These results indicate that IL-6 and TNF-α, post-menopausal state, and steroids produce osteoporosis by an unidentified mechanism. Pro-inflammatory cytokines, estrogen, and steroids bring about their actions by influencing the metabolism of essential fatty acids (EFAs). I propose that EFAs and their metabolites act as second messengers of actions of corticosteroids, cytokines, and estrogen. This implies that EFAs are of benefit in the prevention and management of osteoporosis. This argument is supported by the observation that plasma phospholipid content of unsaturated fatty acids is decreased in those with osteoporosis. The reports that long-chain metabolites of EFAs including arachidonic acid, docosahexaenoic acid and eicosapentaenoic acid, and lipoxin A4 are of benefit in the prevention and management of osteoporosis lends further support to this proposal.

The Dysregulation of Essential Fatty Acid (EFA) Metabolism May Be a Factor in the Pathogenesis of Sepsis.

I propose that a deficiency of essential fatty acids (EFAs) and an alteration in their (EFAs) metabolism could be a major factor in the pathogenesis of sepsis and sepsis-related mortality. The failure of corticosteroids, anti-TNF-α, and anti-interleukin-6 monoclonal antibodies can be attributed to this altered EFA metabolism in sepsis. Vitamin C; folic acid; and vitamin B1, B6, and B12 serve as co-factors necessary for the activity of desaturase enzymes that are the rate-limiting steps in the metabolism of EFAs. The altered metabolism of EFAs results in an imbalance in the production and activities of pro- and anti-inflammatory eicosanoids and cytokines resulting in both hyperimmune and hypoimmune responses seen in sepsis. This implies that restoring the metabolism of EFAs to normal may form a newer therapeutic approach both in the prevention and management of sepsis and other critical illnesses.

Unveiling the optimal path: High-pressure homogenization and D-phase emulsification methods for borage oil nanoemulsion design

Borage oil contains high levels of essential omega-6 fatty acids, which are important for skin structure and function. For this reason, this oil can be used for the treatment of cutaneous diseases including atopic dermatitis. This disease is associated with an abnormality in essential fatty acids (EFAs) metabolism, particularly in the production of gamma-linolenic acid, leading to impaired incorporation of EFAs into the phospholipid membrane. EFAs bioavailability can be enhanced by using a borage oil nano-based drug delivery system. In this study a borage oil nanoemulsion was prepared using high-pressure homogenization (HPH) and D-phase emulsification (DPE), respectively, high and low energy methods. A design space approach was performed to optimize the formulations. The optimized HPH nanoemulsion (HPH-NE) presented a particle size and zeta potential (ZP) of 425.3 ± 5.6 nm, and − 19.4 ± 3.7 mV, respectively. For the DPE nanoemulsion (DPE-NE) the particle size was 334.4 ± 5.2 nm, and the zeta potential was − 34.6 ± 1.0 mV. Furthermore, DPE-NE presented higher toxicity compared to HPH-NE, possibly related to the presence of the polyol. These nanoemulsions may improve the borage oil bioavailability for oral administration. Thus, they can be used as an adjuvant therapy in the treatment of atopic dermatitis.

Plasma essential fatty acid on hospital admission is a marker of COVID-19 disease severity

It is important for allocation of resources to predict those COVID patients at high risk of dying or organ failure. Early signals to initiate cellular events of host immunity can be derived from essential fatty acid metabolites preceding the cascade of proinflammatory signals. Much research has focused on understanding later proinflammatory responses. We assessed if remodelling of plasma phospholipid content of essential fatty acids by the COVID-19 virus provides early markers for potential death and disease severity. Here we show that, at hospital admission, COVID-19 infected subjects who survive exhibit higher proportions of C20:4n-6 in plasma phospholipids concurrent with marked proinflammatory cytokine elevation in plasma compared to healthy subjects. In contrast, more than half of subjects who die of this virus exhibit very low C18:2n-6 and C20:4n-6 content in plasma phospholipids on hospital admission compared with healthy control subjects. Moreover, in these subjects who die, the low level of primary inflammatory signals indicates limited or aberrant stimulation of host immunity. We conclude that COVID-19 infection results in early fundamental remodelling of essential fatty acid metabolism. In subjects with high mortality, it appears that plasma n-6 fatty acid content is too low to stimulate cellular events of host immunity.

Predicted essential fatty acid intakes for a group of dairy cows also apply at individual animal level

The ruminant requirements for essential fatty acids (EFAs), particularly linoleic acid (LA) and alpha-linolenic acid (ALA), have not been fully determined, although evidence suggests that an adequate supply of polyunsaturated fatty acids (FAs) could improve immunity and reproduction in transition cows. In previous studies, we predicted EFA intake for a group of cows based on animal characteristics and milk EFA secretions. However, to support precision livestock feeding, we need to match the nutrient requirements and intakes of each cow as closely as possible. Our group-level predictions may not be accurate enough to estimate the EFA intake of an individual cow, due to inter-individual variations in EFA digestion and metabolism related to differences in feed intake, intake patterns, and the composition and functioning of the rumen microbiota. To address this issue, here we set out to establish specific equations that predict EFA intake for an individual cow based on the difference (i.e. the residuals) between observed EFA intake and the predicted EFA intake based on our group-level equations. We studied a database of individual dairy cows (26 experiments; 503 datapoints from three research teams) and we predicted the residuals from (1) dietary and animal-related factors (i.e. full predictions) and (2) animal-related factors only (i.e. field predictions), which are considered more field-amenable. The variance of predicted LA and log ALA intake was explained to 68% by observed LA intake and 66% by observed log ALA intake, respectively. The residuals of LA intake were predicted by dietary ALA content, total FA intake, BW, milk yield and fat content in full predictions, and by BW, feeding level, milk yield and fat content, and sum of milk C4:0 to C14:0 FA in field predictions. The log residuals of ALA intake were predicted by dietary NDF and total FA contents, NDF intake, BW, milk protein, LA and ALA contents, and fat yield in full predictions, and by BW, DM intake, milk LA and ALA contents, and fat yield in field predictions. The field predictions showed a moderate loss of accuracy compared to full predictions based on RMSE of prediction (from 38 to 54 g/d for LA and from 0.090 to 0.12 log (g/d) for ALA). This work is the first to predict the EFA intake of an individual cow based on previously established group-level predictions of EFA intake adjusted for dietary and animal-related factors.

Protein-Energy Malnutrition during Gestation and Lactation in Rats Affects Growth Rate, Brain Development and Essential Fatty Acid Metabolism

The influence of feeding a low protein diet to rat dams during gestation and lactation on lipid metabolism in pups was studied. Wistar rats were fed 5, 10, 15 and 25% dietary protein during gestation and lactation. Pup growth was monitored until weaning, and brain weight, protein concentration, proteolipid concentration and total lipid phosphorus concentration of brain were analyzed. The levels of fatty acids in dam milk as well as in pup liver phospholipids and brain prosphatidylcholine and phosphatidylethanolamine were determined. The progressive deprivation of maternal dietary protein produced a reduction in the total saturated fatty acid concentration of dam milk and an increment in the concentration of nonmetabolized linoleic acid. Pup body and brain weights as well as proteolipid, protein and total lipid phosphorus concentrations in brain were reduced in proportion to the degree of dietary protein deficiency. The products:precursor ratio of (n-6) fatty acids in liver phospholipids revealed an impairment in the elongation-desaturation pathway due to maternal protein deficiency. Both (n-6) and (n-3) polyunsaturated fatty acids within brain phosphatidylethanolamine were decreased by reduced maternal dietary protein intake, whereas only the linoleic acid-derived products were similarly affected in the corresponding phosphatidylcholine fraction. These results demonstrate the widespread and profound deleterious effects of low protein levels of maternal diet on the growth rate, brain development and fatty acid metabolism of rat pups.

Essential Fatty Acid Deficiency in Cystic Fibrosis Disease Progression: Role of Genotype and Sex.

Adequate intake of nutrients such as essential fatty acids (EFA) are critical in cystic fibrosis (CF). The clinical course of deterioration of lung function in people with CF has been shown to relate to nutrition. Independent of the higher energy consumption and malabsorption due to pancreatic insufficiency, EFA deficiency is closely associated with the risk of pulmonary infection, the most significant pathology in CF. This review will focus on the EFA deficiency identified in people with CF, as well as the limited progress made in deciphering the exact metabolic pathways that are dysfunctional in CF. Specifically, people with CF are deficient in linoleic acid, an omega 6 fatty acid, and the ratio of arachidonic acid (omega 6 metabolite) and docosahexaenoic acid (omega 3 metabolite) is increased. Analysis of the molecular pathways in bronchial cells has identified changes in the enzymes that metabolise EFA. However, fatty acid metabolism primarily occurs in the liver, with EFA metabolism in CF liver not yet investigated, indicating that further research is required. Despite limited understanding in this area, it is well known that adequate EFA concentrations are critical to normal membrane structure and function, and thus are important to consider in disease processes. Novel insights into the relationship between CF genotype and EFA phenotype will be discussed, in addition to sex differences in EFA concentrations in people with CF. Collectively, investigating the specific effects of genotype and sex on fatty acid metabolism may provide support for the management of people with CF via personalised genotype- and sex-specific nutritional therapies.

Metabolism of linoleic and linolenic acids in muscle cells of two freshwater fish with n-3 or n-6 fatty acid requirements

Different fish species have specific requirements for essential fatty acids (EFAs). However, it is not well known whether cellular EFAs metabolism patterns among fish species are related to their differences in EFA requirements. In the present study, we used primary muscle cells from grass carp (GCM) and Nile tilapia (NTM), which has specific requirement of n-3 and n-6 EFA, respectively, to compare the fatty acids uptake, β-oxidation and esterification towards [1-14C]-labeled linoleic acid (LA, 18:2n-6) and linolenic acid (LNA, 18:3n-3). The results showed that the uptake rate of LNA was significantly (P < 0.05) higher than LA in GCM, but lower than LA in NTM. Total mitochondrial and peroxisomal β-oxidation efficiencies for LA were also significantly higher than those for LNA in GCM, while the opposite trend was observed in NTM. In GCM, the esterification of LNA into triacylglycerol (TG) was significantly lower than that of LA, but higher LNA esterification into phosphatidylcholine (PC) than LA was observed. However, the significantly higher LA esterification into TG and PC was observed in NTM. Additionally, LNA significantly upregulated the expressions of the genes related to lipid transportation, while significantly downregulated the expressions of the genes related to lipid catabolism in GCM. However, in NTM, the LA significantly upregulated the expressions of the genes related to lipid transportation, but did not change the expressions of the genes related to lipid catabolism and lipogenesis. In conclusion, GCM had specific preference to uptake and esterify LNA and tends to breakdown LA, while NTM preferred to uptake and esterify LA and tended to breakdown LNA. These differences are in accordance with the specific EFA requirements of grass carp and Nile tilapia. Our present study provides new information for understanding the specific EFA requirements of different fish species from the perspective of cellular EFAs metabolism.

Marginal Zinc Deficiency Alters Essential Fatty Acid Metabolism in Healthy Men

BackgroundRice biofortification with Zinc (Zn) can improve the Zn status of rice-consuming populations. However, the metabolic impact in humans consuming Zn-biofortified rice is unknown. ObjectivesTo determine the effects of Zn-biofortified rice on lipid metabolism in normolipidemic men. MethodsThe men consumed a rice-based diet containing 6 mg Zn/d and 1.5 g phytate (phytate/Zn ratio = 44) for 2 wk followed by a 10-mg Zn/d diet without phytate for 4 wk. An ad libitum diet supplemented with 25 mg Zn/d was then fed for 3 wk. Fasting blood samples were taken at baseline and at the end of each metabolic period for measuring plasma zinc, glucose, insulin, triglyceride (TG), LDL and HDL cholesterol, fatty acids, oxylipins, and fatty acid desaturase activities. Statistical differences were assessed by linear mixed model. ResultsFatty acid desaturase (FADS) 1 activity decreased by 29.1% (P = 0.007) when the 6-mg Zn/d diet was consumed for 2 wk. This change was associated with significant decreases in HDL and LDL cholesterol. The alterations in FADS1, HDL cholesterol, and TG remained unchanged when Zn intakes were increased to 10 mg/d for 4 wk. Supplementation with 25 mg Zn/d for 3 wk normalized these metabolic changes and significantly increased LDL cholesterol at the end of this metabolic period compared with baseline. FADS1 activity was inversely correlated with FADS2 (rmcorr = –0.52; P = 0.001) and TG (rmcorr = –0.55; P = 0.001) at all time points. ConclusionsA low-zinc, high-phytate rice-based diet reduced plasma HDL cholesterol concentrations and altered fatty acid profiles in healthy men within 2 wk. Consuming 10 mg Zn/d without phytate for 4 wk did not improve the lipid profiles, but a 25-mg Zn/d supplement corrects these alterations in lipid metabolism within 3 wk.

必須脂肪酸の代謝による免疫・アレルギー・炎症の制御

必須脂肪酸の代謝による免疫・アレルギー・炎症の制御

The Partitioning of Newly Assimilated Linoleic and α-Linolenic Acids Between Synthesis of Longer-Chain Polyunsaturated Fatty Acids and Hydroxyoctadecaenoic Acids Is a Putative Branch Point in T-Cell Essential Fatty Acid Metabolism.

Longer-chain polyunsaturated fatty acids (LCPUFAs) ≥20 carbons long are required for leukocyte function. These can be obtained from the diet, but there is some evidence that leukocytes can convert essential fatty acids (EFAs) into LCPUFAs. We used stable isotope tracers to investigate LCPUFA biosynthesis and the effect of different EFA substrate ratios in human T lymphocytes. CD3+ T cells were incubated for up to 48 h with or without concanavalin A in media containing a 18:2n-6:18:3n-3 (EFA) ratio of either 5:1 or 8:1 and [13C]18:3n-3 plus [d5]18:2n-6. Mitogen stimulation increased the amounts of 16:1n-7, 18:1n-9, 18:2n-6, 20:3n-6, 20:4n-6, 18:3n-3, and 20:5n-3 in T cells. Expression of the activation marker CD69 preceded increased FADS2 and FADS1 mRNA expression and increased amounts of [d5]20:2n-6 and [13C]20:3n-3 at 48 h. In addition, 22-carbon n-6 or n-3 LCPUFA synthesis was not detected, consistent with the absence of ELOVL2 expression. An EFA ratio of 8:1 reduced 18:3n-3 conversion and enhanced 20:2n-6 synthesis compared to a 5:1 ratio. Here, [d5]9- and [d5]-13-hydroxyoctadecadienoic (HODE) and [13C]9- and [13C]13-hydroxyoctadecatrienoic acids (HOTrE) were the major labelled oxylipins in culture supernatants; labelled oxylipins ≥20 carbons were not detected. An EFA ratio of 8:1 suppressed 9- and 13-HOTrE synthesis, but there was no significant effect on 9- and 13-HODE synthesis. These findings suggest that partitioning of newly assimilated EFA between LCPUFA synthesis and hydroxyoctadecaenoic acid may be a metabolic branch point in T-cell EFA metabolism that has implications for understanding the effects of dietary fats on T lymphocyte function.

Zinc Supplements Taken with Food Increase Essential Fatty Acid Desaturation Indices in Adult Men Compared with Zinc Taken in the Fasted State

BackgroundZinc intake is associated with reduced risk of metabolic disease in adults, possibly due in part to zinc's role in essential fatty acid (EFA) desaturation. Although plasma zinc is the accepted indicator of zinc status, product-to-precursor activity indices of fatty acid desaturase (FADS) 1 and 2 have also been proposed as response indicators for changes in zinc intake. ObjectivesTo examine zinc supplement effects on plasma zinc concentration (PZC) and estimated FADS 1 and 2 activities, when zinc supplements are taken with food compared with fasted. MethodsApparently healthy adult men were randomly allocated to take 25 mg zinc as zinc gluconate either in the fasted state 30 min before breakfast [zinc before breakfast (ZBB)] or with breakfast [zinc with breakfast (ZWB)] daily for 13 d. Fasting PZC was measured by inductively coupled plasma optical emission spectrometry. Selected EFAs for FADS activity indices were measured by LC-MS/MS at study baseline and end. ResultsA total of 35 men completed the study (ZBB, n = 18; ZWB, n = 17). Mean ± SEM PZC was 86.2 ± 1.64 μg/dL at baseline. After 2 wk of zinc supplementation, the PZCs were 18% higher in the ZBB compared with the ZWB groups (105 ± 5.88 compared with 88.7 ± 2.36 μg/dL, P = < 0.05). However, the geometric mean (95% CI) FADS1 activity indices were 15% higher in the ZWB than the ZBB participants, 6.45 (5.84, 7.13) compared with 5.57 (5.05, 6.14), P < 0.05. ConclusionsThese data demonstrate a lack of congruence between the effects of zinc supplements on PZC and EFA metabolism in response to whether a zinc supplement is taken with or without food. Additional research is needed to determine how absorbed zinc may be directed differently toward metabolic processes, when coabsorbed with food. This trial was registered at clinicaltrials.gov as NCT03619421.

Effect of fat diet on essential fatty acid metabolism of neutral lipids in rat blood serum

Aim. To determine the effect of dietary fats on the content and metabolism of polyunsaturated fatty acids (PUFA) in the fraction of neutral lipids blood serum.Methods. The effect of sunflower, high oleic sunflower (HOSO) and palm oils was studied when feeding rats with diets with 5 % fat for 30 days. Rats fed a fat-free diet (FFD) served as a control. The fatty acid composition of neutral blood serum lipids was determined by gas chromatography. The “activity” of fatty acid biosynthesis enzymes: elongase and desaturases was calculated from the ratio of the content of fatty acids.Results. A high content of PUFA was found in rats treated with FFD. Feeding rats with a diet with 5 % sunflower oil increased the total content of PUFAs with a slight decrease in the level of ω-3 PUFAs. Feeding rats with diets containing 5 % palm oil or HOSO did not affect the total content of PUFA, but increased the content of ω-3 PUFA. A very high "activity" of stearyl-CoA desaturase was found in rats fed FFD and fat diets. The consumption of HOSO inhibits the formation of arachidonic acid, while the consumption of palm oil enhances it.Conclusions. A high level of PUFA in neutral lipids in the blood serum of rats may indicate the presence of endogenous sources of PUFA. The optimal (for rats) consumption of dietary fats has a small effect on the content and metabolism of PUFA, with the exception of sunflower oil, the consumption of which significantly increases the ω-6/ω-3 PUFA ratio.

Induction of Beneficial Changes in Glucose Homeostasis, Lipid Profile, Inflammation, Retinopathy, Bile Acids and Gut Microbiota in Streptozotocin-Induced Type 1 Diabetes Mellitus by Essential Fatty Acids

Background: Essential fatty acids (EFAs) n3 alpha-linolenic acid (ALA) and n6 linoleic acid (LA) have been shown to improve lipid metabolism, promote nervous system development, suppress inflammation, and are of benefit in diabetes mellitus and cancer. But the exact mechanism of their action(s) is not clear. In the present study, we evaluated the effects of ALA and LA on glucose homeostasis, circulating lipid profile, inflammatory markers, gut microbiome, and bile acids in streptozotocin (STZ)-induced type 1 diabetes with retinopathy in rats. We also measured vitreal LXA4 levels in patients with diabetic retinopathy since arachidonic acid (AA), the precursor of LXA4, is derived from LA. Methods: The study was performed in male Sprague Dawley rats. Type 1 DM was induced by intraperitoneal injection of STZ. The type 1 DM animals received LA or ALA 100 ug/day via intraperitoneal route on alternate days till the end of the study (21 days after the DM onset). In these animals, glucose homeostasis and lipid profile were evaluated. Plasma and retinal fatty acid profile by gas chromatography (GC), retinal histology by H&E staining, activities of desaturases in the retina and liver tissues and inflammatory markers by qRT-PCR, and composition of the gut microbiota by 16S rDNA sequencing technology of the fecal samples were performed. In addition, short-chain fatty acids (SCFAs) and bile acids (BAs) in the feces and liver of rats were assayed by GC and liquid chromatography coupled with tandem mass spectrometry (UHPLC–MS/MS), respectively. Human vitreal samples obtained from patients with proliferative diabetic retinopathy (PDR) were analyzed for their fatty acids profile and LXA4 levels and compared with those with macular hole (control). Findings: LA and ALA-treated STZ-induced type 1 DM animals showed significant reduction in their plasma glucose levels, pro-inflammatory cytokines (IL-6 and TNF-α), changes in the composition of gut microbiome in the form of an increase in the abundance of Ruminococcaceae (ALA-treated group), Alloprevotella, Prevotellaceae_Ga6A1_group, Ruminococcaceae_UCG_010 and Ruminococcus_1 (in LA-treated group) , an increase in acetic acid and butyric acid, and an increase in the fecal concentrations of CA, CDCA and TUDCA and a decrease in GCA. Concentrations of hepatic CDCA, TCDCA, and TUDCA were significantly increased in ALA treated animals while CDCA were elevated in those with LA treatment. STZ-treated animals showed significant decrease in plasma LA, GLA, and AA and ALA levels with no significant changes in retinal fatty acid composition. All these changes reverted to normal in LA and ALA treated group. The changes in the plasma fatty acid composition were accompanied by significant alterations in the expression of desaturases, COX-2 and 5-LOX and 12-LOX enzymes and pro- and anti-inflammatory cytokines. In addition, retinal LXA4 levels were found to be decreased in patients with PDR. Interpretation: The results of the present study suggest that ALA and LA administration can improve plasma glucose levels, suppress inflammation, and produce significant beneficial alterations in the gut microbiota, plasma lipid profile and EFAs metabolism. Decrease in retinal LXA4 levels in those with PDR agree with the suggestion that EFAs metabolism is altered in T1DM and DR. These results imply a significant role for EFAs and their metabolites in the pathobiology of type 1 DM and diabetic retinopathy. Funding Information: The project was funded by the National Natural Science Foundation of China (No. 82000886), and Natural Science Foundation of Zhejiang Province (No.LQ20H120011). Declaration of Interests: Authors have no conflicts of interest to declare. Ethics Approval Statement: This study was approved by the animal ethics committee of the Second Affiliated Hospital of Zhejiang University school of medicine. All experimental procedures using animals were performed in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. This study was approved by the Clinical Ethical Research Committee of the Second Affiliated Hospital of Zhejiang University school of medicine. The study was performed as per the tenets of Helsinki declaration. Informed consent obtained from all the participating patients.

The Role of GPR120 Receptor in Essential Fatty Acids Metabolism in Schizophrenia.

A growing body of evidence confirms abnormal fatty acid (FAs) metabolism in the pathophysiology of schizophrenia. Omega-3 polyunsaturated fatty acids (PUFAs) are endogenous ligands of the G protein-coupled receptors, which have anti-inflammatory properties and are a therapeutic target in many diseases. No clinical studies are concerned with the role of the GPR120 signaling pathway in schizophrenia. The aim of the study was to determine the differences in PUFA nutritional status and metabolism between patients with schizophrenia (SZ group) and healthy individuals (HC group). The study included 80 participants (40 in the SZ group, 40 in the HC group). There were no differences in serum GPR120 and PUFA concentrations and PUFA intake between the examined groups. In the HC group, there was a relationship between FAs in serum and GPR120 concentration (p < 0.05): α-linolenic acid (ALA) (R = −0.46), docosahexaenoic acid (DHA) (R = −0.54), omega-3 PUFAs (R = −0.41), arachidonic acid (AA) (R = −0.44). In the SZ group, FA serum concentration was not related to GPR120 (p > 0.05). In the HC group, ALA and DHA serum concentrations were independently associated with GPR120 (p < 0.05) in the model adjusted for eicosapentaenoic acid (EPA) and accounted for 38.59% of GPR120 variability (p < 0.05). Our results indicate different metabolisms of FAs in schizophrenia. It is possible that the diminished anti-inflammatory response could be a component connecting GPR120 insensitivity with schizophrenia.

Serum metabolic changes associated with dioxin exposure in a Chinese male cohort

Dioxins, a group of persistent organic pollutants, have been proved to correlate with ranges of diseases by activating the aryl hydrocarbon receptor (AhR). However, previous dioxin toxicity studies primarily focused on the activation of AhR with signaling pathways at gene and protein levels. The investigation of underlying mechanisms at the metabolic level is still necessary. In this study, serum samples of 48 and 47 healthy participants with the highest and lowest dioxin levels based on quartile distribution of the serum dioxin concentrations of 215 male adults were selected for metabolomics analysis by using liquid chromatography coupled with orbitrap high-resolution mass spectrometry to investigate dioxin-related metabolic responses. The identified potential biomarkers included acylcarnitines, fatty acids and derivatives, glycerophospholipids, etc. suggested that metabolic pathways such as fatty acid β-oxidation, essential fatty acid metabolism, arachidonic acid metabolism, glycerophospholipid and sphingolipid metabolism and purine metabolism were disturbed by dioxin exposure. The results indicated that people with high dioxin exposure levels were at the potential health risks of inflammation, liver and cardiovascular diseases. The metabolic findings may help understand the link between dioxin exposure and the diseases.

Omega-3 fatty acid supplementation for cystic fibrosis.

Omega-3 fatty acid supplementation for cystic fibrosis.

Bioactive Lipids in Age-Related Disorders.

Our own studies and those of others have shown that defects in essential fatty acid (EFA) metabolism occurs in age-related disorders such as obesity, type 2 diabetes mellitus, hypertension, atherosclerosis, coronary heart disease, immune dysfunction and cancer. It has been noted that in all these disorders there could occur a defect in the activities of desaturases, cyclo-oxygenase (COX), and lipoxygenase (LOX) enzymes leading to a decrease in the formation of their long-chain products gamma-linolenic acid (GLA), arachidonic acid, eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). This leads to an increase in the production of pro-inflammatory prostaglandin E2 (PGE2), thromboxanes (TXs), and leukotrienes (LTs) and a decrease in anti-inflammatory lipoxin A4, resolvins, protectins and maresins. All these bioactive molecules are termed as bioactive lipids (BALs). This imbalance in the metabolites of EFAs leads to low-grade systemic inflammation and at times acute inflammatory events at specific local sites that trigger the development of various age-related disorders such as obesity, type 2 diabetes mellitus, hypertension, coronary heart disease, atherosclerosis, and immune dysfunction as seen in rheumatoid arthritis, lupus, nephritis and other localized inflammatory conditions. This evidence implies that methods designed to restore BALs to normal can prevent age-related disorders and enhance longevity and health.

Commentary on Zhao et al Manuscript Entitled: "Quantitative Association Between Serum/Dietary Magnesium and Cardiovascular Disease/Coronary Heart Disease Risk: A Dose-Response Meta-analysis of Prospective Cohort Studies": Magnesium and Cardiovascular Disease.

Commentary on Zhao et al Manuscript Entitled: "Quantitative Association Between Serum/Dietary Magnesium and Cardiovascular Disease/Coronary Heart Disease Risk: A Dose-Response Meta-analysis of Prospective Cohort Studies": Magnesium and Cardiovascular Disease.

Metabolism of linoleic and linolenic acids in hepatocytes of two freshwater fish with different n-3 or n-6 fatty acid requirements

The requirements of essential fatty acids (EFAs) varies among fish species, however, the possible different cellular metabolism patterns of EFAs among fish species have not been well addressed. In the present study, we compared activities of cellular FA uptake, β-oxidation and esterification towards [1–14C]-labeled linoleic acid (LA, 18:2n-6) and linolenic acid (LNA, 18:3n-3) in the primary hepatocytes between grass carp (GCH) and Nile tilapia (NTH), which are two freshwater fish but have specific requirement of LNA or LA, respectively. The results showed that LNA had a higher FA-serum binding efficiency than LA in both GCH and NTH. GCH preferentially took up LNA, while NTH primarily took up LA. Both GCH and NTH had higher β-oxidation activity to LA than to LNA. LNA caused higher esterification than LA in GCH, but LA and LNA caused similar esterification effects in NTH. In GCH, LNA tended to induce higher expressions of the genes related to lipid transportation and lipogenesis, but lowered expressions of the lipid catabolism-related genes. However, the regulation of LNA or LA on gene expressions in NTH was marginal. Taken together, GCH had specific preference to take up and esterify LNA, while NTH preferentially took up LA. These differences are in accordance with the specific EFA requirements of grass carp and Nile tilapia. Our study provides new information for understanding the relationships between the specific EFA requirements and cellular metabolism of EFAs in fish.