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 pati...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.展开更多
Background: Isoleucine(Ile) has been implicated in the regulation of energy homeostasis and adipogenesis.However,the impact of surplus dietary Ile intake on muscle lipogenesis remains unknown.The present study aimed t...Background: Isoleucine(Ile) has been implicated in the regulation of energy homeostasis and adipogenesis.However,the impact of surplus dietary Ile intake on muscle lipogenesis remains unknown.The present study aimed to investigate the impact of dietary supplementation of extra-Ile on lipogenesis,fatty acid profile and lipid accumulation in skeletal muscle in finishing pigs.Methods: Forty-eight barrows with initial body weight of 77.0 ± 0.1 kg were allotted to one of two groups and fed diets containing 0.39%,0.53% standardized ileal digestible(SID) Ile with six replicates per treatment and four pigs per replicate for 30 d.Results: Dietary Ile intake significantly improved the intramuscular fat(IMF) content and monounsaturated fatty acid(MUFA) concentration in the skeletal muscle(P < 0.05),and decreased the drip loss and shear force(P < 0.05) without influencing the growth performance of pigs(P > 0.05).Moreover,the phosphorylation of adenosine monophosphate activated protein kinase α(AMPKα) and acetyl coenzyme A carboxylase(ACC) proteins that monitor lipid metabolism were decreased in skeletal muscle of pigs offered extra-Ile diet(P < 0.05).The mRNA expression of adipose-specific genes adipocyte determination and differentiation factor 1(ADD1),fatty acid synthase(FAS),and stearoyl-CoA desaturase(SCD) were upregulated and the activity of SCD was increased as well(P < 0.05).Conclusions: Surplus dietary Ile intake could increase IMF accumulation and MUFA synthesis in skeletal muscle through depressing the phosphorylation of AMPKα-ACC and stimulating the expression and activity of SCD,and increasing the capability of lipogenesis in skeletal muscle.展开更多
Long-chain acyl-Co A synthetase(ACSL) family members include five different ACSL isoforms, each encoded by a separate gene and have multiple spliced variants. ACSLs on endoplasmic reticulum and mitochondrial outer mem...Long-chain acyl-Co A synthetase(ACSL) family members include five different ACSL isoforms, each encoded by a separate gene and have multiple spliced variants. ACSLs on endoplasmic reticulum and mitochondrial outer membrance catalyze fatty acids with chain lengths from 12 to 20 carbon atoms to form acyl-Co As, which are lipid metabolic intermediates and involved in fatty acid metabolism, membrane modifications and various physiological processes. Gain- or lossof-function studies have shown that the expression of individual ACSL isoforms can alter the distribution and amount of intracellular fatty acids. Changes in the types and amounts of fatty acids, in turn, can alter the expression of intracellular ACSLs. ACSL family members affect not only the proliferation of normal cells, but the proliferation of malignant tumor cells. They also regulate cell apoptosis through different signaling pathways and molecular mechanisms. ACSL members have individual functions in fatty acid metabolism in different types of cells depending on substrate preferences, subcellular location and tissue specificity, thus contributing to liver diseases and metabolic diseases, such as fatty liver disease, obesity, atherosclerosis and diabetes. They are also linked to neurological disorders and other diseases. However, the mechanisms are unclear. This review addresses new findings in the classification and properties of ACSLs and the fatty acid metabolismassociated effects of ACSLs in diseases.展开更多
This study investigated the impacts of the degree of unsaturation (unsaturity) of long-chain fatty acids on volatile fatty acid (VFA) profiles of rumen fermentation in vitro. Six types of long-chain fatty acids, i...This study investigated the impacts of the degree of unsaturation (unsaturity) of long-chain fatty acids on volatile fatty acid (VFA) profiles of rumen fermentation in vitro. Six types of long-chain fatty acids, including stearic acid (C18:0, control group), oleic acid (C18:1, n-9), linoleic acid (C18:2, n-6), a-linolenic acid (C18:3, n-3), arachidonic acid (C20:4, n-6) and eicosapentaenoic acid (C20:5, n-3), were tested. Rumen fluid from three goats fitted with ruminal fistulae was used as inoculum and the inclusion rate of long-chain fatty acid was at 3% (w/w) of substrate. Samples were taken for VFA analysis at 0, 3, 6, 9, 12, 18 and 24 h of incubation, respectively. The analysis showed that there were significant differences in the total VFA among treatments, sampling time points, and treatment×time point interactions (P〈0.01). a-Linolenic acid had the highest total VFA (P〈0.01) among different long-chain fatty acids tested. The molar proportion of acetate in total VFA significantly differed among treatments (P〈0.01) and sampling time points (P〈0.01), but not treatment×time point interactions (P〉0.05). In contrast, the molar proportion of propionate did not differ among treatments during the whole incubation (P〉0.05). However, for butyrate molar proportions, significant differences were found not only among sampling time points but also among treatments and treatment×time point interactions (P〈0.01), with eicosapentaenoic acid having the highest value (P〈0.01). Additionally, no statistically significant differences were found in the acetate to propionate ratios among treatments groups (P〉0.05), even the treatments stearic acid and a-linolenic acid were numerically higher than the others. The inclusion of 3% long-chain unsaturated fatty acids differing in the degree of unsaturation brought out a significant quadratic regression relation between the total VFA concentration and the double bond number of fatty acid. In conclusion, the a-linolenic acid with 3 double bonds appeared better for improving rumen microbial fermentation and the total VFA concentration.展开更多
Background: Supplementation of feed with long-chain fatty acids(LCFAs) during the grower and finisher phases has long been discussed as a growth promotion strategy in pigs, but its effects are inconsistent. The purpos...Background: Supplementation of feed with long-chain fatty acids(LCFAs) during the grower and finisher phases has long been discussed as a growth promotion strategy in pigs, but its effects are inconsistent. The purpose of our study was to comprehensively evaluate its effects on the growth performance based on the average daily gain(ADG), average daily feed intake(ADFI) and gain: feed(G:F) ratio and to unveil the roles of the basal diet, LCFA concentration and LCFA saturation.Results: We searched the Pub Med and Web of Science databases(articles published from Jan 1 st, 2000, to Sep 30 th,2018;restricted to English) and compared LCFA-supplemented diets with control diets. We retrieved 2346 studies, 18 of which(1314 pigs, 26 records) were eligible for our analysis. We used a random-effects model to calculate the weighted mean differences(WMDs) and 95% confidence intervals(CIs). LCFA supplementation in the grower-finisher phase improved the ADG(WMD = 41.74 g/d, 95% CI: 8.81 to 74.66, P = 0.013) and G:F ratio(WMD = 0.019, 95% CI: 0.006 to 0.032, P = 0.003). For supplementation solely in the finisher phase, we found a similar performance in the ADG(WMD = 39.93 g/d, 95% CI: 26.48 to 53.38, P < 0.001) and G:F ratio(WMD = 0.019, 95% CI: 0.006 to 0.032, P < 0.001) but a reduction in the ADFI(WMD =-83.863 g/d, 95% CI:-156.157 to-11.569, P = 0.023). Specifically, approximately 5%LCFA supplementation in the finisher phase had significant effects on the ADG(WMD = 51.385 g/d, 95% CI: 35.816 to66.954, P < 0.001), ADFI(WMD =-102.869 g/d, 95% CI:-189.236 to-16.502, P = 0.02) and G:F ratio(WMD = 0.028, 95%CI: 0.018 to 0.039, P < 0.001), whereas a concentration of approximately 1% exhibited no effects.Conclusions: Overall, regardless of the basal diet and saturation, LCFA supplementation greatly improves the growth performance of grower and finisher pigs, primarily by increasing the energy density.展开更多
The marine microalga Nannochloropsis sp.contains various elongases and desaturases that are critical for biosynthesis of polyunsaturated fatty acids.A full-length cDNA encoding a long-chain fatty acid elongase,named N...The marine microalga Nannochloropsis sp.contains various elongases and desaturases that are critical for biosynthesis of polyunsaturated fatty acids.A full-length cDNA encoding a long-chain fatty acid elongase,named Ns FAE,was cloned from Nannochloropsis sp..The open reading frame of Ns FAE(GenBank accession no.MF680548)consisted of 1068 bp and encoded a predicted protein of 355 amino acids with molecular mass 38.8 k Da.The deduced polypeptide showed 43%–44%identity to fatty acyl elongases from other algae.RT-PCR experiments indicated that the Ns FAE gene exhibited the highest expression in Nannochloropsis sp.at 72 h(i.e.,during the third growth stage)and the expression was significantly lower in the other four growth stages.Plasmid p Ns FAE-CRISPR and a recombinant DNA fragment(ADH1p-Ns FAE-CYCt)were transformed into Saccharomyces cerevisiae strain BY4742 using the CRISPR-Cas system.Yeast transformants containing Ns FAE produced three fatty acids not normally present in wild-type BY4742-linoleic acid,linolenic acid and eicosadienoic acid-indicating that Ns FAE encodes a functional elongase enzyme.展开更多
This study investigated the effects of the degree of unsaturation(unsaturity) of long-chain fatty acids on microbial protein content and the activities of transaminases and dehydrogenase in vitro using goat rumen fl...This study investigated the effects of the degree of unsaturation(unsaturity) of long-chain fatty acids on microbial protein content and the activities of transaminases and dehydrogenase in vitro using goat rumen fluid as the cultural medium.Six types of fatty acids,stearic acid(C18:0,group A,control group),oleic acid(C18:1,n-9,group B),linoleic acid(C18:2,n-6,group C),α-linolenic acid(C18:3,n-3,group D),arachidonic acid(C20:4,n-6,group E),and eicosapentaenoic acid(C20:5,n-3,group F),were tested,and the inclusion ratio of each fatty acid was 3%(w/w) in total of culture substrate.Samples were taken at 0,3,6,9,12,18 and 24 h,respectively,during culture for analyses.Compared with stearic acid,linoleic acid,a-linolenic acid,and arachidonic acid increased the bacterial protein content,while oleic acid and eicosapentaenoic acid had no significant effects;the protozoal protein content was reduced for all the unsaturated fatty acids,and the magnitude of the reduction appeared to be associated with the degree of unsaturity of fatty acids.The total microbial protein content was dominantly accounted by the protozoal protein content(about 4-9 folds of the bacterial protein),and only increased by linoleic acid,but reduced by oleic acid,arachidonic acid and eicosapentaenoic acid.There were no significant effects in the activities of both glutamic oxaloacetic transaminase(GOT) and glutamic-pyruvic transaminase(GPT) for all the other fatty acids,except for arachidonic acid which enhanced GOT activity and oleic acid which enhanced GPT activity.The total dehydrogenase activity was positively correlated with the degree of unsaturation of fatty acids.In conclusion,the inclusion of 3%of long-chain unsaturated fatty acids increased bacterial protein content,whereas reduced protozoal protein content and enhanced dehydrogenase activity.The fatty acids with more than three double bonds had detrimental effects on the microbial protein content.This work demonstrates for the first time the effect rule of the unsaturation degree of long-chain fatty acids on the rumen microbial protein in vitro.展开更多
Long-chain acyl coenzyme A synthetase(ACSL) is a member of the synthetase family encoded by a multigene family;it plays an important role in the absorption and transport of fatty acid.Here we review the roles of ACSL ...Long-chain acyl coenzyme A synthetase(ACSL) is a member of the synthetase family encoded by a multigene family;it plays an important role in the absorption and transport of fatty acid.Here we review the roles of ACSL in the regulating absorption and transport of fatty acid,as well as the connection between ACSL and some metabolic diseases.展开更多
The extraction of rare earths by long-chain fatty acid in kerosene from sulphate system was described.It was demonstrated from the experimental results that the ratio of kerosene: fatty acid: isooctanol = 55 : 30: 15 ...The extraction of rare earths by long-chain fatty acid in kerosene from sulphate system was described.It was demonstrated from the experimental results that the ratio of kerosene: fatty acid: isooctanol = 55 : 30: 15 ( V/V),By the saturation capability method and the slope method, the extracted reaction mechanism of the extraction of rare earth was studied.It is shown that the extraction reaction conform to the cation exchange reaction mechanism.The extracted sequence of rare earth was determined in this system and it is shown that there is no tetrad effect and the position of yttrium is between lanthanum and cerium.展开更多
Rationally tailored lipid nanoparticles(LNPs)with efficient and tunable delivery of mRNA in vivo are crucial for mRNA vaccines.Selective expression of antigenic protein in lymphoid tissues/organs could improve the imm...Rationally tailored lipid nanoparticles(LNPs)with efficient and tunable delivery of mRNA in vivo are crucial for mRNA vaccines.Selective expression of antigenic protein in lymphoid tissues/organs could improve the immunostimulatory efficacy and safety of LNPs-based mRNA vaccines.Inspired by the metabolic behavior that long-chain saturated fatty acids tending to enter lymphoid tissue rather than the liver,we developed fatty acid-doped LNPs capable of mediating differential protein expressions in the liver and spleen when administered intravenously.When the molar ratio of saturated fatty acid located 60%–70%,the doped LNPs achieved the spleen selective mRNA translation.The mechanism could be attributed to the different cellular uptake behaviors of saturated fatty acids in hepatocytes.Immunization with a model antigen(ovalbumin)mRNA-loaded spleen selective LNPs,we observed enhanced antigen-specific T cell immune responses,and potent immunotherapeutic and immunoprophylactic efficacy in the mouse lymphoma model.Our natural long-chain saturated fatty acids metabolic characteristics-inspired design of LNPs for spleen-selective mRNA vaccines delivery will provide references for designing mRNA vaccines with high efficacy and safety for tumor immunotherapy.展开更多
Fatty acids are energy substrates and cell components which participate in regulating signal transduction,transcription factor activity and secretion of bioactive lipid mediators.The acyl-CoA synthetases(ACSs)family c...Fatty acids are energy substrates and cell components which participate in regulating signal transduction,transcription factor activity and secretion of bioactive lipid mediators.The acyl-CoA synthetases(ACSs)family containing 26 family members exhibits tissue-specific distribution,distinct fatty acid substrate preferences and diverse biological functions.Increasing evidence indicates that dysregulation of fatty acid metabolism in the liver-gut axis,designated as the bidirectional relationship between the gut,microbiome and liver,is closely associated with a range of human diseases including metabolic disorders,inflammatory disease and carcinoma in the gastrointestinal tract and liver.In this review,we depict the role of ACSs in fatty acid metabolism,possible molecular mechanisms through which they exert functions,and their involvement in hepatocellular and colorectal carcinoma,with particular attention paid to long-chain fatty acids and small-chain fatty acids.Additionally,the liver-gut communication and the liver and gut intersection with the microbiome as well as diseases related to microbiota imbalance in the liver-gut axis are addressed.Moreover,the development of potentially therapeutic small molecules,proteins and compounds targeting ACSs in cancer treatment is summarized.展开更多
Fatty acids with different chain length were deoxygenated in the absence of hydrogen (caprylic acid (CA), lauric acid (LA) and stearic acid (SA)). The catalytic tests were carried over Pd-containing catalysts out in a...Fatty acids with different chain length were deoxygenated in the absence of hydrogen (caprylic acid (CA), lauric acid (LA) and stearic acid (SA)). The catalytic tests were carried over Pd-containing catalysts out in a batch reactor under inert gas for 6 h at 250°C to 350°C and pressures from 18 to 75 bar in the absence of additionally fed hydrogen. Pd-containing catalysts were tested;the best performing catalyst was 10% Pd/C with 63% undecane yield at 327°C. These catalysts were used for a comparative decarboxylation of CA, LA and SA. At equal reaction conditions (300°C, 6 h), the chain length of the fatty acid had a strong impact on the conversion, which was steadily increasing, whereas the alkane selectivity ran through a maximum. This work demonstrated the usability of Pd-containing catalysts for the decarboxylation of various fatty acids in the absence of additionally fed hydrogen with respect to the manufacture of hydrocarbons that can be used as blending components for fuels.展开更多
The clinical implications of non-alcoholic fatty liver diseases(NAFLD)derive from their potential to progress to fibrosis and cirrhosis.Inappropriate dietary fat intake,excessive intake of soft drinks,insulin resistan...The clinical implications of non-alcoholic fatty liver diseases(NAFLD)derive from their potential to progress to fibrosis and cirrhosis.Inappropriate dietary fat intake,excessive intake of soft drinks,insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride(TG)accumulation.An olive oil-rich diet decreases accumulation of TGs in the liver,improves postprandial TGs,glucose and glucagonlike peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver.The principal mechanisms include:decreased nuclear factor-kappaB activation,decreased lowdensity lipoprotein oxidation,and improved insulin resistance by reduced production of inflammatory cytokines(tumor necrosis factor,interleukin-6)and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1.The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids,mainly from olive oil.In this review,we describe the dietary sources of the monounsaturated fatty acids,the composition of olive oil,dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis,clinical and experimental studies that assess the relationship between olive oil and NAFLD,and the mechanism by which olive oil ameliorates fatty liver,and we discuss future perspectives.展开更多
Long-chain acyl-coenzyme A(CoA)synthase 4(ACSL4)is an enzyme that esterifies CoA into specific polyunsaturated fatty acids,such as arachidonic acid and adrenic acid.Based on accumulated evidence,the ACSL4-catalyzed bi...Long-chain acyl-coenzyme A(CoA)synthase 4(ACSL4)is an enzyme that esterifies CoA into specific polyunsaturated fatty acids,such as arachidonic acid and adrenic acid.Based on accumulated evidence,the ACSL4-catalyzed biosynthesis of arachidonoyl-CoA contributes to the execution of ferroptosis by triggering phospholipid peroxidation.Ferroptosis is a type of programmed cell death caused by iron-dependent peroxidation of lipids;ACSL4 and glutathione peroxidase 4 positively and negatively regulate ferroptosis,respectively.In addition,ACSL4 is an essential regulator of fatty acid(FA)metabolism.ACSL4 remodels the phospholipid composition of cell membranes,regulates steroidogenesis,and balances eicosanoid biosynthesis.In addition,ACSL4-mediated metabolic reprogramming and antitumor immunity have attracted much attention in cancer biology.Because it facilitates the cross-talk between ferroptosis and FA metabolism,ACSL4 is also a research hotspot in metabolic diseases and ischemia/reperfusion injuries.In this review,we focus on the structure,biological function,and unique role of ASCL4 in various human diseases.Finally,we propose that ACSL4 might be a potential therapeutic target.展开更多
基金Supported by Brazilian Agencies:Conselho Nacional de Desenvolvimento Científico e TecnológicoPrograma Nacional de Cooperação Acadêmica/Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorand Fundação de AmparoàPesquisa do Estado do Rio Grande do Sul.
文摘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.
基金supported by the National Key Research and Development Program of China(2018YFD0500402)the National Natural Science Foundation of China(No.31672431)the National Key Research and Development Program(2016YFD0700201)
文摘Background: Isoleucine(Ile) has been implicated in the regulation of energy homeostasis and adipogenesis.However,the impact of surplus dietary Ile intake on muscle lipogenesis remains unknown.The present study aimed to investigate the impact of dietary supplementation of extra-Ile on lipogenesis,fatty acid profile and lipid accumulation in skeletal muscle in finishing pigs.Methods: Forty-eight barrows with initial body weight of 77.0 ± 0.1 kg were allotted to one of two groups and fed diets containing 0.39%,0.53% standardized ileal digestible(SID) Ile with six replicates per treatment and four pigs per replicate for 30 d.Results: Dietary Ile intake significantly improved the intramuscular fat(IMF) content and monounsaturated fatty acid(MUFA) concentration in the skeletal muscle(P < 0.05),and decreased the drip loss and shear force(P < 0.05) without influencing the growth performance of pigs(P > 0.05).Moreover,the phosphorylation of adenosine monophosphate activated protein kinase α(AMPKα) and acetyl coenzyme A carboxylase(ACC) proteins that monitor lipid metabolism were decreased in skeletal muscle of pigs offered extra-Ile diet(P < 0.05).The mRNA expression of adipose-specific genes adipocyte determination and differentiation factor 1(ADD1),fatty acid synthase(FAS),and stearoyl-CoA desaturase(SCD) were upregulated and the activity of SCD was increased as well(P < 0.05).Conclusions: Surplus dietary Ile intake could increase IMF accumulation and MUFA synthesis in skeletal muscle through depressing the phosphorylation of AMPKα-ACC and stimulating the expression and activity of SCD,and increasing the capability of lipogenesis in skeletal muscle.
基金Supported by National Natural Science Foundation of China,No.81373465
文摘Long-chain acyl-Co A synthetase(ACSL) family members include five different ACSL isoforms, each encoded by a separate gene and have multiple spliced variants. ACSLs on endoplasmic reticulum and mitochondrial outer membrance catalyze fatty acids with chain lengths from 12 to 20 carbon atoms to form acyl-Co As, which are lipid metabolic intermediates and involved in fatty acid metabolism, membrane modifications and various physiological processes. Gain- or lossof-function studies have shown that the expression of individual ACSL isoforms can alter the distribution and amount of intracellular fatty acids. Changes in the types and amounts of fatty acids, in turn, can alter the expression of intracellular ACSLs. ACSL family members affect not only the proliferation of normal cells, but the proliferation of malignant tumor cells. They also regulate cell apoptosis through different signaling pathways and molecular mechanisms. ACSL members have individual functions in fatty acid metabolism in different types of cells depending on substrate preferences, subcellular location and tissue specificity, thus contributing to liver diseases and metabolic diseases, such as fatty liver disease, obesity, atherosclerosis and diabetes. They are also linked to neurological disorders and other diseases. However, the mechanisms are unclear. This review addresses new findings in the classification and properties of ACSLs and the fatty acid metabolismassociated effects of ACSLs in diseases.
基金financially supported by the Graduate Student Innovation Project of Jiangsu Province,China (KYLX15_1377)the Natural Science Foundation of Jiangsu Province,China (BK20151312)the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD),China
文摘This study investigated the impacts of the degree of unsaturation (unsaturity) of long-chain fatty acids on volatile fatty acid (VFA) profiles of rumen fermentation in vitro. Six types of long-chain fatty acids, including stearic acid (C18:0, control group), oleic acid (C18:1, n-9), linoleic acid (C18:2, n-6), a-linolenic acid (C18:3, n-3), arachidonic acid (C20:4, n-6) and eicosapentaenoic acid (C20:5, n-3), were tested. Rumen fluid from three goats fitted with ruminal fistulae was used as inoculum and the inclusion rate of long-chain fatty acid was at 3% (w/w) of substrate. Samples were taken for VFA analysis at 0, 3, 6, 9, 12, 18 and 24 h of incubation, respectively. The analysis showed that there were significant differences in the total VFA among treatments, sampling time points, and treatment×time point interactions (P〈0.01). a-Linolenic acid had the highest total VFA (P〈0.01) among different long-chain fatty acids tested. The molar proportion of acetate in total VFA significantly differed among treatments (P〈0.01) and sampling time points (P〈0.01), but not treatment×time point interactions (P〉0.05). In contrast, the molar proportion of propionate did not differ among treatments during the whole incubation (P〉0.05). However, for butyrate molar proportions, significant differences were found not only among sampling time points but also among treatments and treatment×time point interactions (P〈0.01), with eicosapentaenoic acid having the highest value (P〈0.01). Additionally, no statistically significant differences were found in the acetate to propionate ratios among treatments groups (P〉0.05), even the treatments stearic acid and a-linolenic acid were numerically higher than the others. The inclusion of 3% long-chain unsaturated fatty acids differing in the degree of unsaturation brought out a significant quadratic regression relation between the total VFA concentration and the double bond number of fatty acid. In conclusion, the a-linolenic acid with 3 double bonds appeared better for improving rumen microbial fermentation and the total VFA concentration.
基金supported by the Key Program of the National Natural Science Foundation of China(grant#3163000269)National Special Fund for Modern Industrial Technology System(grant#CARS-35)Major Science and Technology Special Fund of Zhejiang Province(grant#2015C02022)
文摘Background: Supplementation of feed with long-chain fatty acids(LCFAs) during the grower and finisher phases has long been discussed as a growth promotion strategy in pigs, but its effects are inconsistent. The purpose of our study was to comprehensively evaluate its effects on the growth performance based on the average daily gain(ADG), average daily feed intake(ADFI) and gain: feed(G:F) ratio and to unveil the roles of the basal diet, LCFA concentration and LCFA saturation.Results: We searched the Pub Med and Web of Science databases(articles published from Jan 1 st, 2000, to Sep 30 th,2018;restricted to English) and compared LCFA-supplemented diets with control diets. We retrieved 2346 studies, 18 of which(1314 pigs, 26 records) were eligible for our analysis. We used a random-effects model to calculate the weighted mean differences(WMDs) and 95% confidence intervals(CIs). LCFA supplementation in the grower-finisher phase improved the ADG(WMD = 41.74 g/d, 95% CI: 8.81 to 74.66, P = 0.013) and G:F ratio(WMD = 0.019, 95% CI: 0.006 to 0.032, P = 0.003). For supplementation solely in the finisher phase, we found a similar performance in the ADG(WMD = 39.93 g/d, 95% CI: 26.48 to 53.38, P < 0.001) and G:F ratio(WMD = 0.019, 95% CI: 0.006 to 0.032, P < 0.001) but a reduction in the ADFI(WMD =-83.863 g/d, 95% CI:-156.157 to-11.569, P = 0.023). Specifically, approximately 5%LCFA supplementation in the finisher phase had significant effects on the ADG(WMD = 51.385 g/d, 95% CI: 35.816 to66.954, P < 0.001), ADFI(WMD =-102.869 g/d, 95% CI:-189.236 to-16.502, P = 0.02) and G:F ratio(WMD = 0.028, 95%CI: 0.018 to 0.039, P < 0.001), whereas a concentration of approximately 1% exhibited no effects.Conclusions: Overall, regardless of the basal diet and saturation, LCFA supplementation greatly improves the growth performance of grower and finisher pigs, primarily by increasing the energy density.
基金supported by the Basic Scientific Fund for National Public Research Institutes of China (No. 2016Q07)
文摘The marine microalga Nannochloropsis sp.contains various elongases and desaturases that are critical for biosynthesis of polyunsaturated fatty acids.A full-length cDNA encoding a long-chain fatty acid elongase,named Ns FAE,was cloned from Nannochloropsis sp..The open reading frame of Ns FAE(GenBank accession no.MF680548)consisted of 1068 bp and encoded a predicted protein of 355 amino acids with molecular mass 38.8 k Da.The deduced polypeptide showed 43%–44%identity to fatty acyl elongases from other algae.RT-PCR experiments indicated that the Ns FAE gene exhibited the highest expression in Nannochloropsis sp.at 72 h(i.e.,during the third growth stage)and the expression was significantly lower in the other four growth stages.Plasmid p Ns FAE-CRISPR and a recombinant DNA fragment(ADH1p-Ns FAE-CYCt)were transformed into Saccharomyces cerevisiae strain BY4742 using the CRISPR-Cas system.Yeast transformants containing Ns FAE produced three fatty acids not normally present in wild-type BY4742-linoleic acid,linolenic acid and eicosadienoic acid-indicating that Ns FAE encodes a functional elongase enzyme.
基金financially supported by the Innovation Foundation for Undergraduate of Yangzhou University,China (201311117034)the Domestic Cooperative Innovation ofIndustry-University-Research(XT20140012)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),China
文摘This study investigated the effects of the degree of unsaturation(unsaturity) of long-chain fatty acids on microbial protein content and the activities of transaminases and dehydrogenase in vitro using goat rumen fluid as the cultural medium.Six types of fatty acids,stearic acid(C18:0,group A,control group),oleic acid(C18:1,n-9,group B),linoleic acid(C18:2,n-6,group C),α-linolenic acid(C18:3,n-3,group D),arachidonic acid(C20:4,n-6,group E),and eicosapentaenoic acid(C20:5,n-3,group F),were tested,and the inclusion ratio of each fatty acid was 3%(w/w) in total of culture substrate.Samples were taken at 0,3,6,9,12,18 and 24 h,respectively,during culture for analyses.Compared with stearic acid,linoleic acid,a-linolenic acid,and arachidonic acid increased the bacterial protein content,while oleic acid and eicosapentaenoic acid had no significant effects;the protozoal protein content was reduced for all the unsaturated fatty acids,and the magnitude of the reduction appeared to be associated with the degree of unsaturity of fatty acids.The total microbial protein content was dominantly accounted by the protozoal protein content(about 4-9 folds of the bacterial protein),and only increased by linoleic acid,but reduced by oleic acid,arachidonic acid and eicosapentaenoic acid.There were no significant effects in the activities of both glutamic oxaloacetic transaminase(GOT) and glutamic-pyruvic transaminase(GPT) for all the other fatty acids,except for arachidonic acid which enhanced GOT activity and oleic acid which enhanced GPT activity.The total dehydrogenase activity was positively correlated with the degree of unsaturation of fatty acids.In conclusion,the inclusion of 3%of long-chain unsaturated fatty acids increased bacterial protein content,whereas reduced protozoal protein content and enhanced dehydrogenase activity.The fatty acids with more than three double bonds had detrimental effects on the microbial protein content.This work demonstrates for the first time the effect rule of the unsaturation degree of long-chain fatty acids on the rumen microbial protein in vitro.
基金Supported by the National Natural Science Foundation of China(81373465)
文摘Long-chain acyl coenzyme A synthetase(ACSL) is a member of the synthetase family encoded by a multigene family;it plays an important role in the absorption and transport of fatty acid.Here we review the roles of ACSL in the regulating absorption and transport of fatty acid,as well as the connection between ACSL and some metabolic diseases.
文摘The extraction of rare earths by long-chain fatty acid in kerosene from sulphate system was described.It was demonstrated from the experimental results that the ratio of kerosene: fatty acid: isooctanol = 55 : 30: 15 ( V/V),By the saturation capability method and the slope method, the extracted reaction mechanism of the extraction of rare earth was studied.It is shown that the extraction reaction conform to the cation exchange reaction mechanism.The extracted sequence of rare earth was determined in this system and it is shown that there is no tetrad effect and the position of yttrium is between lanthanum and cerium.
基金supported by the National Key Research and Development Program of China(No.2021YFA1201102)Henan Medical Science and Technology Joint Building Program(No.SBGJ202102132)+2 种基金Henan Province Youth Talent Promoting Project(No.2022HYTP047)the National Natural Science Foundation of China(Nos.82003255,82101385 and 82073231)Key Research and Development Project of Henan Province(No.232102311224)and First-Class Clinical Medicine Discipline Construction Talents Cultivation Project of Zhengzhou University.
文摘Rationally tailored lipid nanoparticles(LNPs)with efficient and tunable delivery of mRNA in vivo are crucial for mRNA vaccines.Selective expression of antigenic protein in lymphoid tissues/organs could improve the immunostimulatory efficacy and safety of LNPs-based mRNA vaccines.Inspired by the metabolic behavior that long-chain saturated fatty acids tending to enter lymphoid tissue rather than the liver,we developed fatty acid-doped LNPs capable of mediating differential protein expressions in the liver and spleen when administered intravenously.When the molar ratio of saturated fatty acid located 60%–70%,the doped LNPs achieved the spleen selective mRNA translation.The mechanism could be attributed to the different cellular uptake behaviors of saturated fatty acids in hepatocytes.Immunization with a model antigen(ovalbumin)mRNA-loaded spleen selective LNPs,we observed enhanced antigen-specific T cell immune responses,and potent immunotherapeutic and immunoprophylactic efficacy in the mouse lymphoma model.Our natural long-chain saturated fatty acids metabolic characteristics-inspired design of LNPs for spleen-selective mRNA vaccines delivery will provide references for designing mRNA vaccines with high efficacy and safety for tumor immunotherapy.
基金Supported by the Interdisziplinäres Zentrum für Klinische Forschung(IZKF-MSP-06)of University Hospital Jena.
文摘Fatty acids are energy substrates and cell components which participate in regulating signal transduction,transcription factor activity and secretion of bioactive lipid mediators.The acyl-CoA synthetases(ACSs)family containing 26 family members exhibits tissue-specific distribution,distinct fatty acid substrate preferences and diverse biological functions.Increasing evidence indicates that dysregulation of fatty acid metabolism in the liver-gut axis,designated as the bidirectional relationship between the gut,microbiome and liver,is closely associated with a range of human diseases including metabolic disorders,inflammatory disease and carcinoma in the gastrointestinal tract and liver.In this review,we depict the role of ACSs in fatty acid metabolism,possible molecular mechanisms through which they exert functions,and their involvement in hepatocellular and colorectal carcinoma,with particular attention paid to long-chain fatty acids and small-chain fatty acids.Additionally,the liver-gut communication and the liver and gut intersection with the microbiome as well as diseases related to microbiota imbalance in the liver-gut axis are addressed.Moreover,the development of potentially therapeutic small molecules,proteins and compounds targeting ACSs in cancer treatment is summarized.
文摘Fatty acids with different chain length were deoxygenated in the absence of hydrogen (caprylic acid (CA), lauric acid (LA) and stearic acid (SA)). The catalytic tests were carried over Pd-containing catalysts out in a batch reactor under inert gas for 6 h at 250°C to 350°C and pressures from 18 to 75 bar in the absence of additionally fed hydrogen. Pd-containing catalysts were tested;the best performing catalyst was 10% Pd/C with 63% undecane yield at 327°C. These catalysts were used for a comparative decarboxylation of CA, LA and SA. At equal reaction conditions (300°C, 6 h), the chain length of the fatty acid had a strong impact on the conversion, which was steadily increasing, whereas the alkane selectivity ran through a maximum. This work demonstrated the usability of Pd-containing catalysts for the decarboxylation of various fatty acids in the absence of additionally fed hydrogen with respect to the manufacture of hydrocarbons that can be used as blending components for fuels.
文摘The clinical implications of non-alcoholic fatty liver diseases(NAFLD)derive from their potential to progress to fibrosis and cirrhosis.Inappropriate dietary fat intake,excessive intake of soft drinks,insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride(TG)accumulation.An olive oil-rich diet decreases accumulation of TGs in the liver,improves postprandial TGs,glucose and glucagonlike peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver.The principal mechanisms include:decreased nuclear factor-kappaB activation,decreased lowdensity lipoprotein oxidation,and improved insulin resistance by reduced production of inflammatory cytokines(tumor necrosis factor,interleukin-6)and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1.The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids,mainly from olive oil.In this review,we describe the dietary sources of the monounsaturated fatty acids,the composition of olive oil,dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis,clinical and experimental studies that assess the relationship between olive oil and NAFLD,and the mechanism by which olive oil ameliorates fatty liver,and we discuss future perspectives.
基金supported by the Key Program of General Program of the National Natural Science Foundation of China(NSFC)(No.81730018)Natural Science Foundation of Hunan Province(No.2021JC0003)
文摘Long-chain acyl-coenzyme A(CoA)synthase 4(ACSL4)is an enzyme that esterifies CoA into specific polyunsaturated fatty acids,such as arachidonic acid and adrenic acid.Based on accumulated evidence,the ACSL4-catalyzed biosynthesis of arachidonoyl-CoA contributes to the execution of ferroptosis by triggering phospholipid peroxidation.Ferroptosis is a type of programmed cell death caused by iron-dependent peroxidation of lipids;ACSL4 and glutathione peroxidase 4 positively and negatively regulate ferroptosis,respectively.In addition,ACSL4 is an essential regulator of fatty acid(FA)metabolism.ACSL4 remodels the phospholipid composition of cell membranes,regulates steroidogenesis,and balances eicosanoid biosynthesis.In addition,ACSL4-mediated metabolic reprogramming and antitumor immunity have attracted much attention in cancer biology.Because it facilitates the cross-talk between ferroptosis and FA metabolism,ACSL4 is also a research hotspot in metabolic diseases and ischemia/reperfusion injuries.In this review,we focus on the structure,biological function,and unique role of ASCL4 in various human diseases.Finally,we propose that ACSL4 might be a potential therapeutic target.