Mapping and identification of QTLs for seed fatty acids in soybean(Glycine max L.)

Soybean is one of the most important sources of vegetable oil.The oil content and fatty acid ratio have attracted significant attention due to their impacts on the shelf-life of soybean oil products and consumer health.In this study,a high-density genetic map derived from Guizao 1 and Brazil 13 was used to analyze the quantitative trait loci of palmitic acid(PA),stearic acid(SA),oleic acid(OA),linoleic acid(LA),linolenic acid(LNA),and oil content(OC).A total of 54 stable QTLs were detected in the genetic map linkage analysis,which shared six bin intervals.Among them,the bin interval on chromosome 13(bin106-bin118 and bin123-bin125)was found to include stable QTLs in multiple environments that were linked to OA,LA,and LNA.Eight differentially expressed genes(DEGs)within these QTL intervals were determined as candidate genes according to the combination of parental resequencing,bioinformatics and RNA sequencing data.All these results are conducive to breeding soybean with the ideal fatty acid ratio for food,and provide the genetic basis for mining genes related to the fatty acid and oil content traits in soybean.

Maternal supplementation with n-3 fatty acids affects placental lipid metabolism, inflammation, oxidative stress, the endocannabinoid system, and the neonate cytokine concentrations in dairy cows

Background The placenta plays a crucial role in supporting and influencing fetal development.We compared the effects of prepartum supplementation with omega-3(n-3)fatty acid(FA)sources,flaxseed oil(FLX)and fish oil(FO),on the expression of genes and proteins related to lipid metabolism,inflammation,oxidative stress,and the endocannabinoid system(ECS)in the expelled placenta,as well as on FA profile and inflammatory response of neonates.Late-pregnant Holstein dairy cows were supplemented with saturated fat(CTL),FLX,or FO.Placental cotyledons(n=5)were collected immediately after expulsion,and extracted RNA and proteins were analyzed by RTPCR and proteomic analysis.Neonatal blood was assessed for FA composition and concentrations of inflammatory markers.Results FO increased the gene expression of fatty acid binding protein 4(FABP4),interleukin 10(IL-10),catalase(CAT),cannabinoid receptor 1(CNR1),and cannabinoid receptor 2(CNR2)compared with CTL placenta.Gene expression of ECS-enzyme FA-amide hydrolase(FAAH)was lower in FLX and FO than in CTL.Proteomic analysis identified 3,974 proteins;of these,51–59 were differentially abundant between treatments(P≤0.05,|fold change|≥1.5).Top canonical pathways enriched in FLX vs.CTL and in FO vs.CTL were triglyceride metabolism and inflammatory processes.Both n-3 FA increased the placental abundance of FA binding proteins(FABPs)3 and 7.The abundance of CNR1 cannabinoid-receptor-interacting-protein-1(CNRIP1)was reduced in FO vs.FLX.In silico modeling affirmed that bovine FABPs bind to endocannabinoids.The FLX increased the abundance of inflammatory CD44-antigen and secreted-phosphoprotein-1,whereas prostaglandin-endoperoxide synthase 2 was decreased in FO vs.CTL placenta.Maternal FO enriched neonatal plasma with n-3 FAs,and both FLX and FO reduced interleukin-6 concentrations compared with CTL.Conclusion Maternal n-3 FA from FLX and FO differentially affected the bovine placenta;both enhanced lipid metabolism and modulated oxidative stress,however,FO increased some transcriptional ECS components,possibly related to the increased FABPs.Maternal FO induced a unique balance of pro-and anti-inflammatory components in the placenta.Taken together,different sources of n-3 FA during late pregnancy enhanced placental immune and metabolic processes,which may affect the neonatal immune system.

Role of short-chain fatty acids in host physiology

Short-chain fatty acids(SCFAs)are major metabolites produced by the gut microbiota through the fermentation of dietary fiber,and they have garnered significant attention due to their close association with host health.As important mediators between the gut microbiota and the host,SCFAs serve as energy substrates for intestinal epithelial cells and maintain homeostasis in host immune and energy metabolism by influencing host epigenetics,activating G protein-coupled receptors,and inhibiting pathogenic microbial infections.This review provides a comprehensive summary of SCFAs synthesis and metabolism and offering an overview of the latest research progress on their roles in protecting gut health,enhancing energy metabolism,mitigating diseases such as cancer,obesity,and diabetes,modulating the gut-brain axis and gut-l ung axis,and promoting bone health.

Electrolyte dependence for the electrochemical decarboxylation of medium-chain fatty acids (n-octanoic acid) into fuel on Pt electrode

The deoxygenation of organic acids, important biomass feedstocks and derivatives, to synthesize hydrocarbon products under mild electrochemical conditions, holds significant importance for the production of carbon-neutral biofuels. There is still limited research on the influential factors of the electrochemical decarboxylation reaction of medium-chain fatty acids. In this study, n-octanoic acid (OA) was chosen as the research subject to investigate the electrochemical decarboxylation behavior of OA on a platinum electrode, focusing on the influence of different alkali metal cations (Li^(+), Na^(+), K^(+)), common anions (SO^(4)^(2−), Cl^(−)), and electrolyte pH. It was found that KOH as an electrolyte exhibited the best performance for OA. Possibly, the larger size of K^(+) increased the alkalinity of the electrode surface, facilitating OA deprotonation. LiOH electrolyte reduced the solubility of OA, thereby inhibiting the decarboxylation reaction. SO^(4)^(2−) exhibited a weak promoting effect on the decarboxylation reaction of OA, while Cl^(−) showed no adverse effect although Cl^(−) may adsorb on the electrode surface. Furthermore, unlike short-chain fatty acids, medium-chain OA can only achieve efficient decarboxylation under alkaline conditions due to its solubility properties. This study provides references and foundations for future efforts to enhance the efficiency of electrochemical decarboxylation synthesis of hydrocarbon biofuels from medium-chain fatty acids.

Expression and clinical significance of short-chain fatty acids in patients with intrahepatic cholestasis of pregnancy

BACKGROUND Intrahepatic cholestasis of pregnancy(ICP)is a pregnancy-specific liver condition that typically arises in the middle and late stages of pregnancy.Short-chain fatty acids(SCFAs),prominent metabolites of the gut microbiota,have significant connections with various pregnancy complications,and some SCFAs hold potential for treating such complications.However,the metabolic profile of SCFAs in patients with ICP remains unclear.AIM To investigate the metabolic profiles and differences in SCFAs present in the maternal and cord blood of patients with ICP and determine the clinical significance of these findings.METHODS Maternal serum and cord blood samples were collected from both patients with ICP(ICP group)and normal pregnant women(NP group).Targeted metabolomics was used to assess the SCFA levels in these samples.RESULTS Significant differences in maternal SCFAs were observed between the ICP and NP groups.Most SCFAs exhibited a consistent declining trend in cord blood samples from the ICP group,mirroring the pattern seen in maternal serum.Correlation analysis revealed a positive correlation between maternal serum SCFAs and cord blood SCFAs[r(Pearson)=0.88,P=7.93e-95].In both maternal serum and cord blood,acetic and caproic acids were identified as key metabolites contributing to the differences in SCFAs between the two groups(variable importance for the projection>1).Receiver operating characteristic analysis demonstrated that multiple SCFAs in maternal blood have excellent diagnostic capabilities for ICP,with caproic acid exhibiting the highest diagnostic efficacy(area under the curve=0.97).CONCLUSION Compared with the NP group,significant alterations were observed in the SCFAs of maternal serum and cord blood in the ICP group,although they displayed distinct patterns of change.Furthermore,the SCFA levels in maternal serum and cord blood were significantly positively correlated.Notably,certain maternal serum SCFAs,specifically caproic and acetic acids,demonstrated excellent diagnostic efficiency for ICP.

Branched-chain fatty acids from goat milk alleviate ulcerative colitis via the TLR4/NF-κB/NLRP3 pathway

Branched-chain fatty acids(BCFAs)are new bioactive fatty acids with anti-inflammatory properties.However,the role of BCFAs in alleviating ulcerative colitis has not been clarified.Herein,we evaluated the protective effect of BCFAs from goat milk in mice with colitis induced using dextran sodium sulfate(DSS)and explored the corresponding mechanism.These results show that BCFAs extracted from goat milk can significantly alleviate weight loss in mice,and reduce the disease activity index and the activity of myeloperoxidase while increasing the content of antioxidant enzymes in colon tissue and reducing the oxidation stress response.These data also show that BCFAs can down-regulate the gene and protein expression of the toll-like receptor 4(TLR4)/nuclear factorκB p65(NF-κB p65)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathway,and at the same time significantly reduce the expression of pro-inflammatory factors tumor necrosis factorα(TNF-α),interleukin 1β(IL-1β),and IL-18 in colon tissue,and significantly increase the expression of the anti-inflammatory factor IL-10.In conclusion,these results demonstrated that BCFAs in goat milk exerted effects on colitis-related inflammatory cytokines and inhibited inflammation by inducing the TLR4/NF-κB/NLRP3 pathway to alleviate DSS-induced ulcerative colitis.This study provides evidence for the potential of BCFAs as bioactive fatty acids in food products and to ameliorate ulcerative colitis development in mice.

Protective effect of long-chain polyunsaturated fatty acids on hepatorenal syndrome in rats

BACKGROUND Hepatorenal syndrome(HRS)is the most prevalent form of acute kidney injury in cirrhotic patients.It is characterized by reduced renal blood flow and represents the most severe complication in cirrhotic patients with advanced disease.Previous research has indicated that antioxidants can delay the onset of a hyperdynamic circulatory state in cirrhosis and improve renal function in HRS patients.Regular omega-3 supplementation has significantly reduced the risk of liver disease.This supplementation could represent an additional therapy for individuals with HRS.AIM To evaluated the antioxidant effect of omega-3 polyunsaturated fatty acid supplementation on the kidneys of cirrhotic rats.METHODS Secondary biliary cirrhosis was induced in rats by biliary duct ligation(BDL)for 28 d.We used 24 male Wistar rats divided into the following groups:I(control);II(treated with omega-3,1 g/kg of body weight);III(BDL treated with omega-3,1 g/kg of body weight);and IV(BDL without treatment).The animals were killed by overdose of anesthetic;the kidneys were dissected,removed,frozen in liquid nitrogen,and stored in a freezer at-80℃for later analysis.We evaluated oxidative stress,nitric oxide(NO)metabolites,DNA damage by the comet assay,cell viability test,and apoptosis in the kidneys.Data were analyzed by one-way analysis of variance,and means were compared using the Tukey test,with P≤0.05.RESULTS Omega-3 significantly decreased the production of reactive oxygen species(P<0.001)and lipoperoxidation in the kidneys of cirrhotic rats treated with omega-3(P<0.001).The activity of the antioxidant enzymes superoxide dismutase and catalase increased in the BDL+omega-3 group compared to the BDL group(P<0.01).NO production,DNA damage,and caspase-9 cleavage decreased significantly in the omega-3-treated BDL group.There was an increase in mitochondrial electrochemical potential(P<0.001)in BDL treated with omega-3 compared to BDL.No changes in the cell survival index in HRS with omega-3 compared to the control group(P>0.05)were observed.CONCLUSION The study demonstrates that omega-3 can protect cellular integrity and function by increasing antioxidant enzymes,inhibiting the formation of free radicals,and reducing apoptosis.

Milk fat globule membrane supplementation protects againstβ-lactoglobul-ininduced food allergy in mice via upregulation of regulatory T cells and enhancement of intestinal barrier in a microbiota-derived short-chain fatty acids manner

Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.

Effects of forsythin extract in Forsythia leaves on intestinal microbiota and short-chain fatty acids in rats fed a high-fat diet

Forsythia suspensa,belonging to the deciduous shrubs of the Luteaceae family,a traditional Chinese medicine,has effects of alleviating swelling,clearing heat,detoxification and promoting blood circulation.The leaves of F.suspensa contain multiple chemical components and have a long history of use in folk medicines and health foods.The purpose of this study was to explore the effects of forsythin extract from F.suspensa leaves on intestinal microbiota and short-chain fatty acid(SCFA)content in rats with obesity induced by a high-fat diet.Forsythin extract in F.suspensa leaves increased the abundance of the intestinal microbiota,ameliorated intestinal microbiota disorders and inhibited the increase in total SCFA content in the intestinal tract in rats with obesity induced by a high-fat diet.These results suggested that forsythin extract in F.suspensa leaves may slow the development of obesity induced by a high-fat diet;thus,its active components and efficacy are worthy of further study.

Development and Production of Omega-3 Fatty Acids-Enriched Foods is an Important Dietary Strategy to Improve People's Nutritional and Health Status

Both Omega-6 and Omega-3 fatty acids are essential nutrients important for cellular structure and function but cannot be synthesized by the human body and must be obtained from food.These two classes of fatty acids are metabolically and functionally different and antagonistically regulate many physiological and pathological processes.Thus,the relative balance between Omega-6 and Omega-3 fatty acids are critical for good health.However,today’s diet contains too much Omega-6 but too little Omega-3,leading to a severe imbalance with a very high Omega-6/Omega-3 ratio(>10)in most people.Many lines of evidence suggest that this imbalance is a key factor contributing to the development of modern chronic diseases.A growing number of studies ranging from laboratory research to clinical trials have shown that balancing the tissue ratio of Omega-6/Omega-3 fatty acids by increasing tissue levels of Omega-3 fatty acids and/or decreasing the content of Omega-6 fatty acids are very beneficial for the prevention and treatment of many life-threating chronic diseases as well as for health promotion of the general public.Therefore,development and production of foods rich in Omega-3-fatty acids should be considered as a key health program to balance essential fat intake and thereby improve the nutritional and health status of all people.

Goat milk-based infant formula regulates intestinal barrier function and promotes the production of short-chain fatty acids

Infant formula(IF)based on cow milk and goat milk is a substitute food for infants who are underfed with human milk.In our previous study,we reported the composition and physicochemical stability of IF based on milk from cows and goats and a combination of both milks.Here,we investigated the effects of these 3 IFs on intestinal immunity and short-chain fatty acid production(SCFAs)using human microbiota-associated(HMA)mice and selected human milk as a positive control.The results showed that goat milk-based IF is associated with a functional immune advantage,due to the rise in the levels of immune-related cytokines interleukin(IL)-2 and IL-10,decreased levels of intestinal permeability markers D-lactic acid and endotoxin,and increased mRNA levels of intestinal tight junction proteins occludin and claudin.In addition,the intestine of mice fed with goat milk-based IF contained 12.06μmol/g acetate,2.42μmol/g propionate,and 1.72μmol/g butyrate,which reached 69%,79%,and 60%of the levels in human milk,respectively.Our results indicate that goat milk-based IF improves intestinal immune function and promotes the production of intestinal SCFAs.

A Review on Tibetan Swine(a)——Carcass,Meat Quality,Basic Nutrition Component,Amino Acids,Fatty Acids,Inosine Monophosphate and Muscle Fiber

In this review, the carcass, meat quality, internal organs, basic nutrition component, amino acids （AAs）, fatty acids, inosine monophosphate （IMP） and mus- cle fiber of Tibetan swine were summarized for the first time. The formation mecha- nism of excellent features was analyzed from the aspects of physiological traits, ge- ographical environments and constraint reasons. Thereby, the outstanding features of Tibetan swine could be extended continuously, and the poor characteristics should be improved in the future.

Free fatty acids receptors 2 and 3 control cell proliferation by regulating cellular glucose uptake

BACKGROUND Colorectal cancer(CRC)is a worldwide problem,which has been associated with changes in diet and lifestyle pattern.As a result of colonic fermentation of dietary fibres,short chain free fatty acids are generated which activate free fatty acid receptors(FFAR)2 and 3.FFAR2 and FFAR3 genes are abundantly expressed in colonic epithelium and play an important role in the metabolic homeostasis of colonic epithelial cells.Earlier studies point to the involvement of FFAR2 in colorectal carcinogenesis.AIM To understand the role of short chain FFARs in CRC.METHODS Transcriptome analysis console software was used to analyse microarray data from CRC patients and cell lines.We employed short-hairpin RNA mediated down regulation of FFAR2 and FFAR3 genes,which was validated using quantitative real time polymerase chain reaction.Assays for glucose uptake and cyclic adenosine monophosphate(cAMP)generation was done along with immunofluorescence studies to study the effects of FFAR2/FFAR3 knockdown.For measuring cell proliferation,we employed real time electrical impedancebased assay available from xCELLigence.RESULTS Microarray data analysis of CRC patient samples showed a significant down regulation of FFAR2 gene expression.This prompted us to study the FFAR2 in CRC.Since,FFAR3 shares significant structural and functional homology with FFAR2,we knocked down both these receptors in CRC cell line HCT 116.These modified cell lines exhibited higher proliferation rate and were found to have increased glucose uptake as well as increased level of glucose transporter 1.Since,FFAR2 and FFAR3 signal through G protein subunit(Gαi),knockdown of these receptors was associated with increased cAMP.Inhibition of protein kinase A(PKA)did not alter the growth and proliferation of these cells indicating a mechanism independent of cAMP/PKA pathway.CONCLUSION Our results suggest role of FFAR2/FFAR3 genes in increased proliferation of colon cancer cells via enhanced glucose uptake and exclude the role of PKA mediated cAMP signalling.Alternate pathways could be involved that would ultimately result in increased cell proliferation as a result of down regulated FFAR2/FFAR3 genes.This study paves the way to understand the mechanism of action of short chain FFARs in CRC.

Preliminary Studies on High-performance Liquid Chro-matography Chemiluminescence Determination of theSaturated Fatty Acids(C_(16) C_(18))in Human Serum

The peroxyoxalate chemiluminescence(CL)detection of fatty acids in human se- rum combined with high-performance liquid chromatography (HPLC)is described.Some fatty acids in serum were extracted with a 1 :1(v/v)mixture of chloroform-n-heptane.2-(4-Hydrazinocarbonyl- phenyl)-4,5-diphenylimidazole (HCPI) was used as a fluorescent labelling reagent of the fatty acids. The labelling reaction was carried out at 30℃ for 1 h at pH 6.5 and the resulting reaction mixture was sudjected to HPLC. The labelled fatty acid C_(17)(P-C_(17))was used as the internal standard. The la- belled fatty acids C_(16) and C_(18) were separated within 18 min on an ODS-8OTM column (150 mm× 6 mm ID,5μm,Tosoh Japan).The calibrlation curves of fatty acids from the spiked control serum were Y_1=-0.003 7 + 0.0028X_1,r=0.994 for FA C_( 16) and Y_2=0.00 1 2 + 0.00098X_2,r=0.999 for FA C_( 18),respectively.The average recoveries of facids from the spiked contrl serum were 107.2%(n=8,RSD=4.3%)for FA C_(16) and 97.35%(n=8, RSD=4.0%)for FA C_(18),respectively.The lower detection limits of fatty acids after reaction were 12μmol per 20μl injection for FA C_(16) and 18 μmol per 20μl injection for FA C_(18),respectively(signal to noise ratio, S/N=2).The HPLC/CL method was applied to the determination of FA C_(16) and FA C_(18) in normal human serum and the results showed that the concentrations of fatty acids in normal human serum were 0.134 ± 0.009 μ mol/ml serum(n=5) for FA C_(16) and 0.052±0.028 μmol/ml serum(n=5)for FA C_(18),respectively.

The Impact of the Essential Fatty Acids (EFA) in Human Health

Linoleic (LA) and α-linolenic acids (ALA) are considered essential fatty acids (EFA) because they are not produced by the human body. This way, EFAs sources must come from the diet. The primary dietary source of n-3 fatty acids is ALA, found in seeds and seed oils. Other important sources are fish oils such as tuna, salmon and herring. Currently, numerous studies suggest possible benefits of essential fatty acids in human health, such as in cardiovascular, cognitive and eye health, and also during pregnancy and childhood. This paper also discusses the impact of fatty acids in human metabolism, and the available evidence regarding its risks. It addresses the relevant debate regarding a general ban of trans fatty acids (TFA) from the world food market, because of the cardiovascular risks associated with its consumption.

Comparative and Computer Assisted Drug Designing of Fatty Acids Isolated from Flowers, Leaves, Stem Bark, Root Bark and Nuts of Semecarpus anacardium L. f. （Anacardiaceae）

Objectives： Computational study will help us in reducing the experimental work. The process of drug discovery involves the designing of molecules with appropriate pharmacophores with the help of various soft wares. The purpose of this paper is to study the probable binding modes of fatty acids on fatty acids after enzymatic hydrolysis of the FAAH （fatty acid amide hydrolase） in different extracts of flowers, leaves, stem bark, root bark and nuts of Semecarpus anacardiurn L. f. by using molecular modeling study and computer assisted drug designing. Nuts yielded 20 fatty acids including saturated, ω-3 unsaturated, ω-6 unsaturated, ω-7 unsaturated and ω-9 unsaturated fatty acids. Based on IR, IH NMR, 13C NMR, MS （mass） spectrometry, GC analysis, the structural elucidation of these isolated fatty acids was established. Methods： A dataset comprising of 20 fatty acids were drawn in ChemDraw and converted into 3D-molecules with all possible tautomers and chiral centers. The minimization of molecules was carried out using PRCG （Polak-Ribiere Conjugate Gradient） method with maximum of 5000 iterations. The minimized compounds were used for protein preparation. The crystal structure of human FAAH （PDB ID： 3K84） is prepared and selected for the docking studies of 20 fatty acids using Schr6dinger docking program module.. Conclusions： In this study, we carried out the molecular docking studies in order to understand the probable binding mode of 20 fatty acids in FAAH from which we identified key active site residues for FAAH, thereby it can be used to design the novel compounds for FAAH targets.

Kinetic analysis of waste activated sludge hydrolysis and short-chain fatty acids production at pH 10

The accumulation of short-chain fatty acids （SCFAs）, a preferred carbon source for enhanced biological phosphorus removal microbes, was significantly improved when waste activated sludge （WAS） was fermented at pH 10. The kinetics of WAS hydrolysis and SCFAs production at pH 10 was investigated. It was observed that during WAS anaerobic fermentation the accumulation of SCFAs was limited by the hydrolysis process, and both the hydrolysis of WAS particulate COD and the accumulation of SCFAs followed first-order kinetics. The hydrolysis and SCFAs accumulation rate constants increased with increasing temperature from 10 to 35℃, which could be described by the Arrhenius equation. The kinetic data further indicated that SCFAs production at pH 10 was a biological process. Compared with the experiment of pH uncontrolled （blank test）, both the rate constants of WAS hydrolysis and SCFAs accumulation at 20℃ were improved significantly when WAS was fermented at pH 10.

Anti-inflammatory properties of the short-chain fatty acids acetate and propionate:A study with relevance to inflammatory bowel disease

AIM： To compare the anti-inflammatory properties of butyrate with two other SCFAs, namely acetate and propionate, which have less well-documented effects on inflammation. METHODS： The effect of SCFAs on cytokine release from human neutrophils was studied with EHSA. SCFA- dependent modulation of NF-κB reporter activity was assessed in the human colon adenocarcinoma cell line, Colo320DM. Finally, the effect of SCFAs on gene expression and cytokine release, measured with RT-PCR and ELISA, respectively, was studied in mouse colon organ cultures established from colitic mice. RESULTS： Acetate, propionate and butyrate at 30 mmol/L decreased LPS-stimulated TNFα release from neutrophils, without affecting IL-8 protein release. All SCFAs dose dependently inhibited NF-κB reporter activity in Colo320DM cells. Propionate dose-dependently suppressed IL-6 mRNA and protein release from colon organ cultures and comparative studies revealed that propionate and butyrate at 30 mmol/L caused a strong inhibition of immune-related gene expression, whereas acetate was less effective. A similar inhibition was achieved with the proteasome inhibitor MG-132, but not the p38 MAPK inhibitor SB203580. All SCFAs decreased IL-6 protein release from organ cultures. CONCLUSION： In the present study propionate and butyrate were equipotent, whereas acetate was less effective, at suppressing NF-κB reporter activity, immune-related gene expression and cytokine release in vitro. Our findings suggest that propionate and acetate, in addition to butyrate, could be useful in the treatment of inflammatory disorders, including IBD.

Effects of different free fatty acids on insulin resistance in rats

BACKGROUND: Much evidence demonstrates that elevated free fatty acids (FFAs) are associated with insulin resistance. However, it is not clear whether different FFAs can cause different degrees of peripheral insulin resistance. This study aimed to investigate the effects of short-term elevation of FFAs on hepatic and peripheral insulin action, and determine whether FFAs with different degrees of saturation have differential effects on hepatic insulin resistance. METHODS: Intralipid+heparin (IH, polyunsaturated fatty acids), oleate (OLE), lard oil+heparin (LOH), and saline (SAL) were separately infused intravenously for 7 hours in normal Wistar rats. During the last 2 hours of the fat/saline infusion, a hyperinsulinemic-euglycemic clamping was performed with [6-H-3] glucose tracer. Plasma glucose was measured using the glucose oxygenase method. Plasma insulin and C-peptide were determined by radioimmunoassays. Plasma FFAs were measured using a colorimetric method. RESULTS: Compared with infusion of SAL, plasma FFA levels were significantly elevated by infusions of IH, OLE, and LOH (P<0.001). All three fat infusions caused remarkably higher hepatic glucose production (HGP) than SAL (P<0.001). OLE and LOH infusions induced much higher HGP than IH (P<0.01). Glucose utilization (GU) was decreased with all three fat infusions relative to SAL (P<0.001), but GU did not differ among the three types of fat infusions. CONCLUSIONS: Short-term elevation of FFAs can induce hepatic and peripheral insulin resistance. Polyunsaturated fatty acids induced less hepatic insulin resistance than monounsaturated or saturated fatty acids. However, IH, OLE, and LOH infusions induced similar peripheral insulin resistance.

A randomized controlled trial of omega-3 fatty acids in dry eye syndrome

AIM:To evaluate the role of dietary supplementation of omega-3 fatty acids in dry eye syndrome.METHODS:A prospective,interventional,placebo controlled,double blind randomized trial was done at two referral eye centers.Two hundred and sixty-four eyes of patients with dry eye were randomized to receive one capsule(500mg)two times a day containing 325mg EPA and 175mg DHA for 3 months(omega-3 group).The omega-3 group was compared to a group of patients(n=254)who received a placebo(placebo group).There were 4 patient visits(at baseline,1 month,2 months and3 months).On each visit,recording of corrected distance visual acuity(CDVA),slit lamp examination and questionnaire based symptom evaluation and scoring was done.A symptomatic score of 0-6 was mild,6.1-12moderate and 12.1-18 severe dry eye.Response to intervention was monitored by routine tear function tests like Schirmer I test,tear film break-up time(TBUT),Rose Bengal staining and most notably,conjunctival impression cytology.RESULTS:Sixty-five percent of patients in the omega-3group and 33%of patients in placebo group had significant improvement in symptoms at 3 months(P=0.005).There was a significant change in both Schirmer’s test value and TBUT values in the omega-3group(P【0.001),both comparisons.However,there was a larger drift in TBUT values in omega-3 than the placebo group,in comparison to Schirmer’s test values.The mean TBUT score was 2.54±2.34 in the omega-3group and 0.13±0.16 in placebo group,respectively.The mean reduction in symptom score in omega-3 group was 2.02±0.96 as compared to 0.48±0.22 in placebogroup(P【0.001).Despite a slight increase mean score,the Schirmer scores did not correlate well with symptomatic improvement.CONCLUSION:Omega-3 fatty acids have a definite role for dry eye syndrome.The benefit seems to be more marked in conditions such as blepharitis and meibomian gland disease.The role of omega fatty acids in tear production and secretion needs further evaluation.